{"count":220363,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1484","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1482","results":[{"created":"2020-12-07T16:50:15.141765+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.27","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: SLC52A3 as Green List (high evidence)","entity_name":"SLC52A3","entity_type":"gene"},{"created":"2020-12-07T16:50:15.131354+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.27","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: slc52a3 has been classified as Green List (High Evidence).","entity_name":"SLC52A3","entity_type":"gene"},{"created":"2020-12-07T16:49:54.089137+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.27","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: SLC52A3 as Green List (high evidence)","entity_name":"SLC52A3","entity_type":"gene"},{"created":"2020-12-07T16:49:54.081586+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.27","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: slc52a3 has been classified as Green List (High Evidence).","entity_name":"SLC52A3","entity_type":"gene"},{"created":"2020-12-07T16:49:32.946007+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.26","user_name":"Bryony Thompson","item_type":"entity","text":"Publications for gene: TRPV4 were set to ","entity_name":"TRPV4","entity_type":"gene"},{"created":"2020-12-07T16:48:54.688471+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.25","user_name":"Bryony Thompson","item_type":"entity","text":"Phenotypes for gene: TRPV4 were changed from  to Auditory neuropathy spectrum disorder; Peripheral neuropathy; Hearing loss","entity_name":"TRPV4","entity_type":"gene"},{"created":"2020-12-07T16:42:14.415338+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.24","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: TRPV4 as Green List (high evidence)","entity_name":"TRPV4","entity_type":"gene"},{"created":"2020-12-07T16:42:14.407939+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.24","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: trpv4 has been classified as Green List (High Evidence).","entity_name":"TRPV4","entity_type":"gene"},{"created":"2020-12-07T16:41:22.895848+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.23","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: TRPV4 as Amber List (moderate evidence)","entity_name":"TRPV4","entity_type":"gene"},{"created":"2020-12-07T16:41:22.884724+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.23","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: trpv4 has been classified as Amber List (Moderate Evidence).","entity_name":"TRPV4","entity_type":"gene"},{"created":"2020-12-07T16:36:56.174161+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.21","user_name":"Bryony Thompson","item_type":"entity","text":"gene: TRPV4 was added\ngene: TRPV4 was added to Deafness_IsolatedAndComplex. Sources: Literature\nMode of inheritance for gene: TRPV4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"TRPV4","entity_type":"gene"},{"created":"2020-12-07T16:27:29.730870+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.20","user_name":"Bryony Thompson","item_type":"entity","text":"gene: SLC52A3 was added\ngene: SLC52A3 was added to Deafness_IsolatedAndComplex. Sources: Literature\nMode of inheritance for gene: SLC52A3 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: SLC52A3 were set to Brown-Vialetto-Van Laere syndrome 1 MIM#211530","entity_name":"SLC52A3","entity_type":"gene"},{"created":"2020-12-07T16:23:42.674325+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Dean Phelan","item_type":"entity","text":"reviewed gene: PEX6: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32399598; Phenotypes: Perrault syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"PEX6","entity_type":"gene"},{"created":"2020-12-07T16:22:16.860882+11:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"0.158","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment on mode of pathogenicity: Dominant negative","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:22:16.841278+11:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"0.158","user_name":"Elena Savva","item_type":"entity","text":"Mode of pathogenicity for gene: VPS4A was changed from None to Other","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:22:14.324994+11:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"0.158","user_name":"Elena Savva","item_type":"entity","text":"changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"; to: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:21:55.822842+11:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"0.158","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: VPS4A as Green List (high evidence)","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:21:55.811995+11:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"0.158","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:21:49.303617+11:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"0.157","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: VPS4A as ready","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:21:49.299704+11:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"0.157","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:21:49.271119+11:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"0.157","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been removed from the panel.","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:21:37.519191+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.19","user_name":"Bryony Thompson","item_type":"entity","text":"gene: NDRG1 was added\ngene: NDRG1 was added to Deafness_IsolatedAndComplex. Sources: Literature\nMode of inheritance for gene: NDRG1 was set to BIALLELIC, autosomal or pseudoautosomal","entity_name":"NDRG1","entity_type":"gene"},{"created":"2020-12-07T16:21:33.290825+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.949","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment on mode of pathogenicity: Dominant negative","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:21:33.249831+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.949","user_name":"Elena Savva","item_type":"entity","text":"Mode of pathogenicity for gene: VPS4A was changed from None to Other","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:20:46.250228+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.948","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: VPS4A as ready","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:20:46.243681+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.948","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:20:46.203661+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.948","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:20:37.329514+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.948","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: VPS4A as Green List (high evidence)","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:20:37.318829+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.948","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:19:01.495369+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.157","user_name":"Elena Savva","item_type":"entity","text":"Deleted their review","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:18:55.391052+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.157","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: VPS4A as ready","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:18:55.386675+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.157","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:18:55.366381+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.157","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:18:52.486154+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.157","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment on mode of pathogenicity: Dominant negative","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:18:52.463170+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.157","user_name":"Elena Savva","item_type":"entity","text":"Mode of pathogenicity for gene: VPS4A was changed from None to Other","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:18:04.331437+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.156","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: VPS4A as Green List (high evidence)","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:18:04.321551+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.156","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:17:06.694057+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"0.508","user_name":"Elena Savva","item_type":"entity","text":"changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:16:32.600359+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"0.508","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment on mode of pathogenicity: Dominant negative","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:16:32.584192+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"0.508","user_name":"Elena Savva","item_type":"entity","text":"Mode of pathogenicity for gene: VPS4A was changed from None to Other","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:16:28.463268+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"0.508","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: VPS4A as ready","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:16:28.453050+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"0.508","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:16:28.414604+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"0.508","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:16:12.837816+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"0.508","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: VPS4A as Green List (high evidence)","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:16:12.827658+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"0.508","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:15:10.717360+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3251","user_name":"Elena Savva","item_type":"entity","text":"changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:14:59.216622+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3251","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment on mode of pathogenicity: Dominant negative","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:14:59.196196+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3251","user_name":"Elena Savva","item_type":"entity","text":"Mode of pathogenicity for gene: VPS4A was changed from None to Other","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:14:42.407698+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3251","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: VPS4A as ready","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:14:42.403621+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3251","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:14:42.375230+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3251","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:14:39.957091+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3251","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: VPS4A as Green List (high evidence)","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:14:39.949222+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3251","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:13:44.677222+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Kristin Rigbye","item_type":"entity","text":"changed review comment from: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. \r\n1x homozygous missense in the MIT domain (milder phenotype and unaffected parents).\r\nDemonstrated defective CD71 trafficking in all 3 patients. \r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the  variants were at amino acid position 284 (changes to Trp and Gly). \r\nDemonstrated that the variants had a dominant-negative effect on VPS4A function.\r\n\"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\" \nSources: Literature; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.\r\n1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).\r\nDemonstrated defective CD71 trafficking in all 3 patients.\r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).\r\nDemonstrated that the variants had a dominant-negative effect on VPS4A function.\r\n\r\n\"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:13:17.636213+11:00","panel_name":"Cerebellar and Pontocerebellar Hypoplasia","panel_id":72,"panel_version":"0.157","user_name":"Kristin Rigbye","item_type":"entity","text":"gene: VPS4A was added\ngene: VPS4A was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature\nMode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: VPS4A were set to 33186543; 33186545\nPhenotypes for gene: VPS4A were set to Neurodevelopmental disorder\nReview for gene: VPS4A was set to GREEN\nAdded comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.\r\n1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).\r\nDemonstrated defective CD71 trafficking in all 3 patients.\r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).\r\nDemonstrated that the variants had a dominant-negative effect on VPS4A function.\r\n\r\n\"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\" \nSources: Literature","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:13:15.667955+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.947","user_name":"Kristin Rigbye","item_type":"entity","text":"gene: VPS4A was added\ngene: VPS4A was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: VPS4A were set to 33186543; 33186545\nPhenotypes for gene: VPS4A were set to Neurodevelopmental disorder\nReview for gene: VPS4A was set to GREEN\nAdded comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.\r\n1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).\r\nDemonstrated defective CD71 trafficking in all 3 patients.\r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).\r\nDemonstrated that the variants had a dominant-negative effect on VPS4A function.\r\n\r\n\"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\" \nSources: Literature","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:13:14.060251+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.155","user_name":"Kristin Rigbye","item_type":"entity","text":"gene: VPS4A was added\ngene: VPS4A was added to Dystonia - complex. Sources: Literature\nMode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: VPS4A were set to 33186543; 33186545\nPhenotypes for gene: VPS4A were set to Neurodevelopmental disorder\nReview for gene: VPS4A was set to GREEN\nAdded comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.\r\n1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).\r\nDemonstrated defective CD71 trafficking in all 3 patients.\r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).\r\nDemonstrated that the variants had a dominant-negative effect on VPS4A function.\r\n\r\n\"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\" \nSources: Literature","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:13:12.669313+11:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"0.507","user_name":"Kristin Rigbye","item_type":"entity","text":"gene: VPS4A was added\ngene: VPS4A was added to Microcephaly. Sources: Literature\nMode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: VPS4A were set to 33186543; 33186545\nPhenotypes for gene: VPS4A were set to Neurodevelopmental disorder\nReview for gene: VPS4A was set to GREEN\nAdded comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.\r\n1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).\r\nDemonstrated defective CD71 trafficking in all 3 patients.\r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).\r\nDemonstrated that the variants had a dominant-negative effect on VPS4A function.\r\n\r\n\"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\" \nSources: Literature","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:13:06.248705+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Kristin Rigbye","item_type":"entity","text":"gene: VPS4A was added\ngene: VPS4A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: VPS4A were set to 33186543; 33186545\nPhenotypes for gene: VPS4A were set to Neurodevelopmental disorder\nReview for gene: VPS4A was set to GREEN\nAdded comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.\r\n1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).\r\nDemonstrated defective CD71 trafficking in all 3 patients.\r\n\r\nPMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).\r\nDemonstrated that the variants had a dominant-negative effect on VPS4A function.\r\n\r\n\"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\" \nSources: Literature","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:13:05.842993+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Elena Savva","item_type":"entity","text":"Deleted their review","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:11:58.731909+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Elena Savva","item_type":"entity","text":"changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.\r\n1x homozygous missense in the MIT domain (milder phenotype and unaffected parents).\r\nDemonstrated defective CD71 trafficking in all 3 patients.\r\n\r\nComment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:03:54.737319+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:03:54.722288+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:03:54.230215+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: VPS4A as ready","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:03:54.224948+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. \"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life.\"","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:03:54.199573+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:03:35.270883+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment on mode of pathogenicity: Dominant negative","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:03:35.256241+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Elena Savva","item_type":"entity","text":"Mode of pathogenicity for gene: VPS4A was changed from Other to Other","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:03:33.640608+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Elena Savva","item_type":"entity","text":"Added comment: Comment on mode of pathogenicity: Dominant negative","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:03:33.579162+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5567","user_name":"Elena Savva","item_type":"entity","text":"Mode of pathogenicity for gene: VPS4A was changed from None to Other","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:03:12.936342+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:03:12.925591+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:03:07.151983+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5566","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: VPS4A as Green List (high evidence)","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:03:07.143941+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5566","user_name":"Elena Savva","item_type":"entity","text":"Gene: vps4a has been classified as Green List (High Evidence).","entity_name":"VPS4A","entity_type":"gene"},{"created":"2020-12-07T16:02:50.705258+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:02:50.695716+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:02:42.030624+11:00","panel_name":"Proteinuria","panel_id":144,"panel_version":"0.148","user_name":"Ain Roesley","item_type":"entity","text":"gene: DAAM2 was added\ngene: DAAM2 was added to Proteinuria. Sources: Literature\nMode of inheritance for gene: DAAM2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: DAAM2 were set to 33232676\nPhenotypes for gene: DAAM2 were set to steroid-resistant nephrotic syndrome (SRNS)\nPenetrance for gene: DAAM2 were set to unknown\nReview for gene: DAAM2 was set to GREEN\nAdded comment: - steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis on histologic analysis of kidney biopsies and foot process effacement shown by electron microscopy (authors have suggested the term nephrotic syndrome type 22 (NPHS22))\r\n- 4 unrelated families, 3 of which were consanguineous\r\n- 4 unique missense and 1 stop\r\n- in vitro studies done for the missense variants \nSources: Literature","entity_name":"DAAM2","entity_type":"gene"},{"created":"2020-12-07T16:02:26.969049+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:02:26.938110+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:02:03.462158+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:02:03.454754+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:01:47.839273+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5565","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: DAAM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33232676; Phenotypes: Steroid-resistant nephrotic syndrome (SRNS); Mode of inheritance: None","entity_name":"DAAM2","entity_type":"gene"},{"created":"2020-12-07T16:01:39.540277+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3249","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:01:39.513408+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3249","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:01:25.353092+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5565","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: DAAM2 as ready","entity_name":"DAAM2","entity_type":"gene"},{"created":"2020-12-07T16:01:25.340586+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5565","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: daam2 has been classified as Green List (High Evidence).","entity_name":"DAAM2","entity_type":"gene"},{"created":"2020-12-07T16:01:18.629533+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:01:18.622385+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3250","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:01:14.859891+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5565","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: DAAM2 were set to ","entity_name":"DAAM2","entity_type":"gene"},{"created":"2020-12-07T16:00:53.488336+11:00","panel_name":"Autism","panel_id":51,"panel_version":"0.123","user_name":"Paul De Fazio","item_type":"entity","text":"gene: BICRA was added\ngene: BICRA was added to Autism. Sources: Literature\nMode of inheritance for gene: BICRA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: BICRA were set to 33232675\nPhenotypes for gene: BICRA were set to Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features\nReview for gene: BICRA was set to GREEN\ngene: BICRA was marked as current diagnostic\nAdded comment: 12 individuals reported, 11 de novo (1 not resolved), \"with neurodevelopmental phenotypes—developmental delay (HP:0001263), intellectual disability (HP:0001249), autism spectrum disorder (HP:0000729), and/or behavioral phenotypes (HP:0000708)—and variable structural birth defects and dysmorphic features\". Mostly LoF or gene deletions, but 2 missense reported. Zebrafish model supports the gene-disease association. \nSources: Literature","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:00:45.277577+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3249","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:00:45.261310+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3249","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:00:30.430279+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5564","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: DAAM2 as Green List (high evidence)","entity_name":"DAAM2","entity_type":"gene"},{"created":"2020-12-07T16:00:30.422036+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.5564","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: daam2 has been classified as Green List (High Evidence).","entity_name":"DAAM2","entity_type":"gene"},{"created":"2020-12-07T16:00:25.789570+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3249","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T16:00:25.779878+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3249","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T15:59:55.071946+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3249","user_name":"Ain Roesley","item_type":"entity","text":"gene: HS2ST1 was added\ngene: HS2ST1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: HS2ST1 were set to 33159882\nPenetrance for gene: HS2ST1 were set to unknown\nAdded comment: - 4 affected from 3 unrelated families\r\n- 3 unique missense and 2 PTCs\r\n- Developmental Delay, Corpus Callosum Hypoplasia or Aplasia, and Skeletal and Renal Abnormalities \nSources: Literature","entity_name":"HS2ST1","entity_type":"gene"},{"created":"2020-12-07T15:59:48.913834+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3249","user_name":"Elena Savva","item_type":"entity","text":"Classified gene: BICRA as Green List (high evidence)","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T15:59:48.855930+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3249","user_name":"Elena Savva","item_type":"entity","text":"Gene: bicra has been classified as Green List (High Evidence).","entity_name":"BICRA","entity_type":"gene"},{"created":"2020-12-07T15:59:43.727559+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3248","user_name":"Elena Savva","item_type":"entity","text":"Marked gene: BICRA as ready","entity_name":"BICRA","entity_type":"gene"}]}