{"count":221304,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=334","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=332","results":[{"created":"2024-12-06T00:05:11.832827+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.335","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ATR-X-related syndrome MONDO:0016980; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)","entity_name":"ATRX","entity_type":"gene"},{"created":"2024-12-06T00:03:56.994642+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.335","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ARX as ready","entity_name":"ARX","entity_type":"gene"},{"created":"2024-12-06T00:03:56.975695+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.335","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: arx has been classified as Green List (High Evidence).","entity_name":"ARX","entity_type":"gene"},{"created":"2024-12-06T00:00:07.218469+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.335","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ARX were changed from  to X-linked lissencephaly with abnormal genitalia, MONDO:0010268","entity_name":"ARX","entity_type":"gene"},{"created":"2024-12-05T23:59:33.280150+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.334","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: ARX were set to ","entity_name":"ARX","entity_type":"gene"},{"created":"2024-12-05T23:58:59.964461+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.333","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: ARX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)","entity_name":"ARX","entity_type":"gene"},{"created":"2024-12-05T23:58:23.762602+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.332","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: 14722918; Phenotypes: X-linked lissencephaly with abnormal genitalia, MONDO:0010268; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)","entity_name":"ARX","entity_type":"gene"},{"created":"2024-12-05T23:52:32.611295+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.332","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: AR as ready","entity_name":"AR","entity_type":"gene"},{"created":"2024-12-05T23:52:32.600223+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.332","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ar has been classified as Green List (High Evidence).","entity_name":"AR","entity_type":"gene"},{"created":"2024-12-05T23:52:26.653568+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.332","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: AR were changed from  to Hypospadias 1, X-linked MIM#30063; Androgen insensitivity MIM#300068; Androgen insensitivity, partial, with or without breast cancer MIM#312300","entity_name":"AR","entity_type":"gene"},{"created":"2024-12-05T23:51:51.063119+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.331","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: AR were set to ","entity_name":"AR","entity_type":"gene"},{"created":"2024-12-05T23:51:19.039499+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.330","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: AR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females","entity_name":"AR","entity_type":"gene"},{"created":"2024-12-05T23:50:44.921651+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.329","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: 22334387; Phenotypes: Hypospadias 1, X-linked MIM#30063, Androgen insensitivity MIM#300068, Androgen insensitivity, partial, with or without breast cancer MIM#312300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females","entity_name":"AR","entity_type":"gene"},{"created":"2024-12-05T23:48:50.299825+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.329","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: AMHR2 as ready","entity_name":"AMHR2","entity_type":"gene"},{"created":"2024-12-05T23:48:50.279551+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.329","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: amhr2 has been classified as Green List (High Evidence).","entity_name":"AMHR2","entity_type":"gene"},{"created":"2024-12-05T23:48:45.831515+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.329","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: AMHR2 were changed from  to Persistent Mullerian duct syndrome, type II MIM#261550","entity_name":"AMHR2","entity_type":"gene"},{"created":"2024-12-05T23:48:14.341065+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.328","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: AMHR2 were set to ","entity_name":"AMHR2","entity_type":"gene"},{"created":"2024-12-05T23:47:40.675501+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.327","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: AMHR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"AMHR2","entity_type":"gene"},{"created":"2024-12-05T23:47:03.969736+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.326","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: AMHR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34810374; Phenotypes: Persistent Mullerian duct syndrome, type II MIM#261550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"AMHR2","entity_type":"gene"},{"created":"2024-12-05T18:53:31.212081+11:00","panel_name":"Spontaneous coronary artery dissection","panel_id":4323,"panel_version":"0.53","user_name":"Stephanie Hesselson","item_type":"entity","text":"reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29650765,33125268,26971055,24303518,19557720,9719186,18992981,26069747,20634758,33969096,28915698; Phenotypes: CORONARY ARTERY DISSECTION SPONTANEOUS MIM#122455, POLYCYSTIC KIDNEY DISEASE 1 WITH OR WITHOUT POLYCYSTIC LIVER DISEASE, PKD1 MIM#173900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"PKD1","entity_type":"gene"},{"created":"2024-12-05T16:54:25.139537+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.242","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21981780, 22508347; Phenotypes: neurodegeneration with brain iron accumulation 4 MONDO:0013674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"C19orf12","entity_type":"gene"},{"created":"2024-12-05T16:36:39.606392+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.242","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: BCAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: 24011989, 28332767, 30713915, 31330203, 32652807; Phenotypes: severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome MONDO:0010334; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females","entity_name":"BCAP31","entity_type":"gene"},{"created":"2024-12-05T16:22:25.697584+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.242","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21094623, 20853184, 20310007; Phenotypes: Kufor-Rakeb syndrome MONDO:0011706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ATP13A2","entity_type":"gene"},{"created":"2024-12-05T16:05:54.894425+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.325","user_name":"Chirag Patel","item_type":"panel","text":"Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Royal Melbourne Hospital; Rare Disease","entity_name":null,"entity_type":null},{"created":"2024-12-05T15:57:13.042388+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.324","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: FREM2 as Green List (high evidence)","entity_name":"FREM2","entity_type":"gene"},{"created":"2024-12-05T15:57:13.018332+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.324","user_name":"Chirag Patel","item_type":"entity","text":"Gene: frem2 has been classified as Green List (High Evidence).","entity_name":"FREM2","entity_type":"gene"},{"created":"2024-12-05T15:56:49.732467+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.324","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: FREM2 as Green List (high evidence)","entity_name":"FREM2","entity_type":"gene"},{"created":"2024-12-05T15:56:49.723035+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.324","user_name":"Chirag Patel","item_type":"entity","text":"Gene: frem2 has been classified as Green List (High Evidence).","entity_name":"FREM2","entity_type":"gene"},{"created":"2024-12-05T15:56:24.906155+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.323","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: FREM2 as Green List (high evidence)","entity_name":"FREM2","entity_type":"gene"},{"created":"2024-12-05T15:56:24.894995+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.323","user_name":"Chirag Patel","item_type":"entity","text":"Gene: frem2 has been classified as Green List (High Evidence).","entity_name":"FREM2","entity_type":"gene"},{"created":"2024-12-05T15:55:57.841891+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.323","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: FRAS1 as Green List (high evidence)","entity_name":"FRAS1","entity_type":"gene"},{"created":"2024-12-05T15:55:57.829270+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.323","user_name":"Chirag Patel","item_type":"entity","text":"Gene: fras1 has been classified as Green List (High Evidence).","entity_name":"FRAS1","entity_type":"gene"},{"created":"2024-12-05T15:55:09.971918+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.322","user_name":"Chirag Patel","item_type":"entity","text":"gene: FRAS1 was added\ngene: FRAS1 was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: FRAS1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: FRAS1 were set to PMID: 12766769, 18671281, 18000968\nPhenotypes for gene: FRAS1 were set to Fraser syndrome 1, MIM#219000\nReview for gene: FRAS1 was set to GREEN\nAdded comment: Fraser syndrome is an autosomal recessive malformation disorder. Major criteria include syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria include anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies. \r\nEstablished gene-disease association. \nSources: Literature","entity_name":"FRAS1","entity_type":"gene"},{"created":"2024-12-05T15:54:45.840687+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.321","user_name":"Chirag Patel","item_type":"entity","text":"gene: FREM2 was added\ngene: FREM2 was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: FREM2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: FREM2 were set to PMID: 15838507, 29688405, 18203166, 18671281, 18000968\nPhenotypes for gene: FREM2 were set to Fraser syndrome 2, MIM#617666\nReview for gene: FREM2 was set to GREEN\nAdded comment: Fraser syndrome is an autosomal recessive malformation disorder. Major criteria include syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria include anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies. \r\nEstablished gene-disease association. \nSources: Literature","entity_name":"FREM2","entity_type":"gene"},{"created":"2024-12-05T15:41:35.146444+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.320","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: SOX2 as Green List (high evidence)","entity_name":"SOX2","entity_type":"gene"},{"created":"2024-12-05T15:41:35.131210+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.320","user_name":"Chirag Patel","item_type":"entity","text":"Gene: sox2 has been classified as Green List (High Evidence).","entity_name":"SOX2","entity_type":"gene"},{"created":"2024-12-05T15:41:00.698478+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.319","user_name":"Chirag Patel","item_type":"entity","text":"gene: SOX2 was added\ngene: SOX2 was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: SOX2 were set to PMID: 20301477\nPhenotypes for gene: SOX2 were set to Anophthalmia/microphthalmia-esophageal atresia syndrome MONDO:0008799; Microphthalmia, syndromic 3, MIM# 206900; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900\nReview for gene: SOX2 was set to GREEN\nAdded comment: SOX2 disorder includes anophthalmia and/or microphthalmia, brain malformations, developmental delay / intellectual disability, oesophageal atresia, pituitary hypoplasia, postnatal growth delay, hypotonia, seizures, and spastic or dystonic movements, and hypogonadotropic hypogonadism (manifest as cryptorchidism and micropenis in males, gonadal dysgenesis infrequently in females, and delayed puberty in both sexes). Established gene-disease association. \nSources: Literature","entity_name":"SOX2","entity_type":"gene"},{"created":"2024-12-05T15:36:12.572881+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.318","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: IRF6 as Green List (high evidence)","entity_name":"IRF6","entity_type":"gene"},{"created":"2024-12-05T15:36:12.558501+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.318","user_name":"Chirag Patel","item_type":"entity","text":"Gene: irf6 has been classified as Green List (High Evidence).","entity_name":"IRF6","entity_type":"gene"},{"created":"2024-12-05T15:35:06.608174+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.242","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301790, 29436738, 30504431, 22345219; Phenotypes: ataxia telangiectasia MONDO:0008840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ATM","entity_type":"gene"},{"created":"2024-12-05T15:33:51.394701+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.317","user_name":"Chirag Patel","item_type":"entity","text":"gene: IRF6 was added\ngene: IRF6 was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: IRF6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: IRF6 were set to PMID: 20301581\nPhenotypes for gene: IRF6 were set to Popliteal pterygium syndrome 1, OMIM #119500\nReview for gene: IRF6 was set to GREEN\nAdded comment: IRF6-related disorders span a spectrum from isolated cleft lip and palate and Van der Woude syndrome (VWS) at the mild end to popliteal pterygium syndrome (PPS) at the more severe end.\r\nEstablished gene-disease association.\r\n\r\nPopliteal pterygium syndrome (PPS) features including orofacial anomalies such as lower lip pits, cleft lip and/or palate, and syngnathia, and skin and genital abnormalities including webbing of the lower limbs, syndactyly, hypoplasia of the labia majora/vagina/uterus, cryptorchidism, and bifid or hypoplastic scrotum. \nSources: Literature","entity_name":"IRF6","entity_type":"gene"},{"created":"2024-12-05T15:28:50.553381+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.316","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: CHD4 as Green List (high evidence)","entity_name":"CHD4","entity_type":"gene"},{"created":"2024-12-05T15:28:50.543479+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.316","user_name":"Chirag Patel","item_type":"entity","text":"Gene: chd4 has been classified as Green List (High Evidence).","entity_name":"CHD4","entity_type":"gene"},{"created":"2024-12-05T15:28:12.372882+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.315","user_name":"Chirag Patel","item_type":"entity","text":"gene: CHD4 was added\ngene: CHD4 was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: CHD4 were set to PMID: 31388190, 32881470\nPhenotypes for gene: CHD4 were set to Sifrim-Hitz-Weiss syndrome, MIM #617159\nReview for gene: CHD4 was set to GREEN\nAdded comment: Sifrim-Hitz-Weiss syndrome is an autosomal dominant intellectual developmental disorder with variable congenital defects affecting other systems, including cardiac, skeletal, and urogenital. Some patients may have short stature, enlarged head circumference, hearing loss, and nonspecific dysmorphic facial features. Established gene-disease association. \r\n\r\nHypogonadism is common in males (cryptorchidism and/or microphallus), with hormonal profile consistent with hypogonadotropic hypogonadism. \nSources: Literature","entity_name":"CHD4","entity_type":"gene"},{"created":"2024-12-05T15:21:21.050219+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.314","user_name":"Chirag Patel","item_type":"entity","text":"gene: POLR1C was added\ngene: POLR1C was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949\nPhenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494\nReview for gene: POLR1C was set to RED\nAdded comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism. \r\n\r\nThiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism. \r\n\r\nGauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene.  Patients too young to comment on hypogonadotropic hypogonadism. \nSources: Literature","entity_name":"POLR1C","entity_type":"gene"},{"created":"2024-12-05T15:20:57.112826+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.314","user_name":"Chirag Patel","item_type":"entity","text":"gene: POLR1C was added\ngene: POLR1C was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949\nPhenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494\nReview for gene: POLR1C was set to RED\nAdded comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism. \r\n\r\nThiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism. \r\n\r\nGauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene.  Patients too young to comment on hypogonadotropic hypogonadism. \nSources: Literature","entity_name":"POLR1C","entity_type":"gene"},{"created":"2024-12-05T15:20:32.661258+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.314","user_name":"Chirag Patel","item_type":"entity","text":"gene: POLR1C was added\ngene: POLR1C was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949, ............22855961\nPhenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494\nReview for gene: POLR1C was set to RED\nAdded comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism. \r\n\r\nThiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism. \r\n\r\nGauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene.  Patients too young to comment on hypogonadotropic hypogonadism. \nSources: Literature","entity_name":"POLR1C","entity_type":"gene"},{"created":"2024-12-05T15:12:41.858791+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.313","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: POLR3B as Green List (high evidence)","entity_name":"POLR3B","entity_type":"gene"},{"created":"2024-12-05T15:12:41.846425+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.313","user_name":"Chirag Patel","item_type":"entity","text":"Gene: polr3b has been classified as Green List (High Evidence).","entity_name":"POLR3B","entity_type":"gene"},{"created":"2024-12-05T15:09:41.433889+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.312","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: POLR3A as Green List (high evidence)","entity_name":"POLR3A","entity_type":"gene"},{"created":"2024-12-05T15:09:41.420772+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.312","user_name":"Chirag Patel","item_type":"entity","text":"Gene: polr3a has been classified as Green List (High Evidence).","entity_name":"POLR3A","entity_type":"gene"},{"created":"2024-12-05T15:09:18.949251+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.312","user_name":"Chirag Patel","item_type":"entity","text":"gene: POLR3B was added\ngene: POLR3B was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: POLR3B were set to PubMed: 27512013, 23355746, 22036171, 22036172, 25339210, 33005949, 22855961\nPhenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism; OMIM #614381\nReview for gene: POLR3B was set to GREEN\nAdded comment: Hypomyelinating leukodystrophy-8 (HLD8) is an autosomal recessive neurologic disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability.\r\n\r\nMultiples families reported with compound heterozygous mutations in POL3RB gene.  \r\n\r\nWolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Delayed puberty/HH, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations. \nSources: Literature","entity_name":"POLR3B","entity_type":"gene"},{"created":"2024-12-05T15:04:58.451598+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.311","user_name":"Chirag Patel","item_type":"entity","text":"gene: POLR3A was added\ngene: POLR3A was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: POLR3A were set to PubMed: 21855841, 25339210, 33005949, 22855961\nPhenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM#607694\nReview for gene: POLR3A was set to GREEN\nAdded comment: Hypomyelinating leukodystrophy-7 (HLD7) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other common features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability.\r\n\r\nBernard et al. (2011) identified 14 different mutations in the POLR3A gene (homozygous or compound heterozygous state), in 19 patients from 12 families. The mutations were spread throughout the gene, and there were no obvious genotype/phenotype correlations. Immunoblot analysis showed decreased levels of POLR3A protein in fibroblasts from 4 affected individuals, and decreased levels in the cortex and cerebral white matter of another patient, suggesting that loss of function is responsible for the disorder. \r\n\r\nWolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Delayed puberty/HH, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations. \nSources: Literature","entity_name":"POLR3A","entity_type":"gene"},{"created":"2024-12-05T14:51:44.105875+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.310","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: HARS2 as Green List (high evidence)","entity_name":"HARS2","entity_type":"gene"},{"created":"2024-12-05T14:51:44.090150+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.310","user_name":"Chirag Patel","item_type":"entity","text":"Gene: hars2 has been classified as Green List (High Evidence).","entity_name":"HARS2","entity_type":"gene"},{"created":"2024-12-05T14:29:07.946567+11:00","panel_name":"Spontaneous coronary artery dissection","panel_id":4323,"panel_version":"0.53","user_name":"Stephanie Hesselson","item_type":"entity","text":"reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39130004; Phenotypes: CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"COL3A1","entity_type":"gene"},{"created":"2024-12-05T14:27:14.161711+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.242","user_name":"Bryony Thompson","item_type":"entity","text":"Publications for gene: KCNQ2 were set to 12742592","entity_name":"KCNQ2","entity_type":"gene"},{"created":"2024-12-05T14:26:51.507120+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.241","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: KCNQ2 as Amber List (moderate evidence)","entity_name":"KCNQ2","entity_type":"gene"},{"created":"2024-12-05T14:26:51.497284+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.241","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: kcnq2 has been classified as Amber List (Moderate Evidence).","entity_name":"KCNQ2","entity_type":"gene"},{"created":"2024-12-05T14:26:18.973375+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.240","user_name":"Bryony Thompson","item_type":"entity","text":"edited their review of gene: KCNQ2: Added comment: Now 2 cases have been reported with dystonic features as part of a complex neurological phenotype.; Changed rating: AMBER; Changed publications: 12742592, 32585800","entity_name":"KCNQ2","entity_type":"gene"},{"created":"2024-12-05T14:23:44.255652+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.309","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: HHAT as Green List (high evidence)","entity_name":"HHAT","entity_type":"gene"},{"created":"2024-12-05T14:23:44.241307+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.309","user_name":"Chirag Patel","item_type":"entity","text":"Gene: hhat has been classified as Green List (High Evidence).","entity_name":"HHAT","entity_type":"gene"},{"created":"2024-12-05T14:23:11.319059+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.308","user_name":"Chirag Patel","item_type":"entity","text":"gene: HHAT was added\ngene: HHAT was added to Differences of Sex Development. Sources: Expert list\nMode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: HHAT were set to PMID: 24784881, 33749989, 35045414\nPhenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome, OMIM:600092\nReview for gene: HHAT was set to GREEN\nAdded comment: 3 individuals from 3 families with 46, XY karyotype and sex reversal, with supportive mouse model reported in 24784881.\r\n\r\nPMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis ( including normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous. They also found that mice lacking functional Hhat show a similar phenotype as the syndromic 46,XY DSD patient including testicular dysgenesis and skeletal defects.\r\n\r\nPMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped thorax, short and angel-shaped epiphyses of hands and feet) and midface retrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a single central incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.)\r\n\r\nPMID: 35045414 - Mazen et al 2022 - report an Egyptian patient with 46,XY DSD (ambiguous genitalia and microcephaly) and a homozygous missense variant in HHAT, which segregated with the phenotype in the family. \nSources: Expert list","entity_name":"HHAT","entity_type":"gene"},{"created":"2024-12-05T14:19:37.738517+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.240","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: APTX: Rating: GREEN; Mode of pathogenicity: None; Publications: 15876520; Phenotypes: ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia MONDO:0008842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"APTX","entity_type":"gene"},{"created":"2024-12-05T14:03:21.443508+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.307","user_name":"Chirag Patel","item_type":"entity","text":"changed review comment from: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.\r\n\r\nPMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.\r\n\r\nPMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.\r\n\r\nPMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease. \r\n\r\nFunctional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs. \r\nSources: Literature; to: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly.\r\n\r\nPMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.\r\n\r\nPMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.\r\n\r\nPMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease. \r\n\r\nFunctional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs. \r\nSources: Literature","entity_name":"CTU2","entity_type":"gene"},{"created":"2024-12-05T14:03:06.565754+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.307","user_name":"Chirag Patel","item_type":"entity","text":"changed review comment from: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.\r\n\r\nMore than 6 families reported, four had the same founder variant. Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs \nSources: Literature; to: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.\r\n\r\nPMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.\r\n\r\nPMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.\r\n\r\nPMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease. \r\n\r\nFunctional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs. \r\nSources: Literature","entity_name":"CTU2","entity_type":"gene"},{"created":"2024-12-05T14:02:11.273844+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.307","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: CTU2 as Green List (high evidence)","entity_name":"CTU2","entity_type":"gene"},{"created":"2024-12-05T14:02:11.263203+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.307","user_name":"Chirag Patel","item_type":"entity","text":"Gene: ctu2 has been classified as Green List (High Evidence).","entity_name":"CTU2","entity_type":"gene"},{"created":"2024-12-05T14:00:40.459979+11:00","panel_name":"Dystonia - complex","panel_id":290,"panel_version":"0.240","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 24262145; Phenotypes: Aicardi-Goutieres syndrome MONDO:0018866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ADAR","entity_type":"gene"},{"created":"2024-12-05T14:00:32.610740+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.306","user_name":"Chirag Patel","item_type":"entity","text":"gene: CTU2 was added\ngene: CTU2 was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CTU2 were set to PMID: 27480277, 26633546, 31301155, 38348206\nPhenotypes for gene: CTU2 were set to DREAM-PL syndrome (Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome), MIM#618142\nReview for gene: CTU2 was set to GREEN\nAdded comment: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.\r\n\r\nMore than 6 families reported, four had the same founder variant. Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs \nSources: Literature","entity_name":"CTU2","entity_type":"gene"},{"created":"2024-12-05T13:46:40.810291+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.305","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: TWNK as Green List (high evidence)","entity_name":"TWNK","entity_type":"gene"},{"created":"2024-12-05T13:46:40.794557+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.305","user_name":"Chirag Patel","item_type":"entity","text":"Gene: twnk has been classified as Green List (High Evidence).","entity_name":"TWNK","entity_type":"gene"},{"created":"2024-12-05T13:46:17.379035+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.305","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: TWNK as Green List (high evidence)","entity_name":"TWNK","entity_type":"gene"},{"created":"2024-12-05T13:46:17.347011+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.305","user_name":"Chirag Patel","item_type":"entity","text":"Gene: twnk has been classified as Green List (High Evidence).","entity_name":"TWNK","entity_type":"gene"},{"created":"2024-12-05T13:45:30.097274+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.304","user_name":"Chirag Patel","item_type":"entity","text":"gene: TWNK was added\ngene: TWNK was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: TWNK was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TWNK were set to PMID: 25355836, 31852434, 31455392\nPhenotypes for gene: TWNK were set to Perrault syndrome 5; MIM# 616138\nReview for gene: TWNK was set to GREEN\nAdded comment: Perrault syndrome-5 (PRLTS5) is an autosomal recessive disorder characterized by progressive ataxia, axonal neuropathy, hyporeflexia, and abnormal eye movements, accompanied by progressive hearing loss and ovarian dysgenesis. \r\n\r\nPMID: 25355836: 4 women from 2 unrelated families with Perrault syndrome-5. \r\n2 sisters in each family presented with primary amenorrhea, lack of secondary sexual characteristics, and gonadal dysgenesis; 2 sisters in 1 family showed streak ovaries. Three of the 4 girls had onset of sensorineural hearing loss at 7 to 8 years of age; the fourth had onset of hearing loss at age 13. All 4 patients developed neurologic involvement in the second or third decades, with features including ataxia, nystagmus, hyporeflexia, and sensory axonal neuropathy with distal sensory impairment. WES identified compound heterozygous variants in each family, but functional studies of the variants were not performed. \r\n\r\nPMID: 31852434: female with severe bilateral hypoacusis, severe ataxia, polyneuropathy, lower limb spastic paraparesis with pyramidal signs, and gonadal dysgenesis, and compound heterozygous variants in TWNK gene (but functional studies of the variants were not performed).  \r\n\r\nPMID: 31455392: 3 siblings from one family with childhood-onset bilateral sensorineural hearing impairment, neurological signs (spinocerebellar ataxia, polyneuropathy), and gonadal dysfunction with early cessation of menses in the 2 females. WES identified compound heterozygous pathogenic mutations in the TWNK gene, which segregated with disease.\r\n, \nSources: Literature","entity_name":"TWNK","entity_type":"gene"},{"created":"2024-12-05T13:34:47.692250+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.303","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: MARS2 as Green List (high evidence)","entity_name":"MARS2","entity_type":"gene"},{"created":"2024-12-05T13:34:47.673927+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.303","user_name":"Chirag Patel","item_type":"entity","text":"Gene: mars2 has been classified as Green List (High Evidence).","entity_name":"MARS2","entity_type":"gene"},{"created":"2024-12-05T13:33:58.402851+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.302","user_name":"Chirag Patel","item_type":"entity","text":"gene: MARS2 was added\ngene: MARS2 was added to Differences of Sex Development. Sources: Expert Review\nMode of inheritance for gene: MARS2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: MARS2 were set to PMID: 27650058, 21464306, 27087618\nPhenotypes for gene: MARS2 were set to Perrault syndrome 2, MIM# 614926\nReview for gene: MARS2 was set to GREEN\nAdded comment: Perrault syndrome-2 (PRLTS2) is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads (ovarian dysgenesis), and infertility, whereas affected males show normal pubertal development and are fertile. No neurological abnormalities reported.\r\n\r\nPMID: 21464306: five affected siblings from one family with three females with ovarian dysgenesis with primary amenorrhea and streak gonads along with sensorineural hearing loss (two males had normal fertility) had two variants in HARS2 with confirmed biparental inheritance. Functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.\r\n\r\nPMID: 27650058: two unrelated probands with Perrault syndrome with profound deafness and secondary amenorrhoea with gonadal dysgenesis were found to have a homozygous variant in HARS2. These probands were not related but were from the same region in Morocco.\r\n\r\nPMID: 27087618: 2 siblings in Turkish family with Perrault syndrome (female sibling had with secondary amenorrhea and gonadal dysgenesis) were found to have a homozygous variant in HARS2. No functional work. \nSources: Expert Review","entity_name":"MARS2","entity_type":"gene"},{"created":"2024-12-05T13:31:52.344131+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.301","user_name":"Chirag Patel","item_type":"entity","text":"gene: HARS2 was added\ngene: HARS2 was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: HARS2 were set to PMID: 27650058, 21464306, 27087618\nPhenotypes for gene: HARS2 were set to Perrault syndrome 2, MIM# 614926\nReview for gene: HARS2 was set to GREEN\nAdded comment: Perrault syndrome-2 (PRLTS2) is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads (ovarian dysgenesis), and infertility, whereas affected males show normal pubertal development and are fertile. No neurological abnormalities reported.\r\n\r\nPMID: 21464306: five affected siblings from one family with three females with ovarian dysgenesis with primary amenorrhea and streak gonads along with sensorineural hearing loss (two males had normal fertility) had two variants in HARS2 with confirmed biparental inheritance. Functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.\r\n\r\nPMID: 27650058: two unrelated probands with Perrault syndrome with profound deafness and secondary amenorrhoea with gonadal dysgenesis were found to have a homozygous variant in HARS2. These probands were not related but were from the same region in Morocco.\r\n\r\nPMID: 27087618: 2 siblings in Turkish family with Perrault syndrome (female sibling had with secondary amenorrhea and gonadal dysgenesis) were found to have a homozygous variant in HARS2. No functional work. \nSources: Literature","entity_name":"HARS2","entity_type":"gene"},{"created":"2024-12-05T13:16:03.026617+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.300","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: LARS2 as Green List (high evidence)","entity_name":"LARS2","entity_type":"gene"},{"created":"2024-12-05T13:16:02.991880+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.300","user_name":"Chirag Patel","item_type":"entity","text":"Gene: lars2 has been classified as Green List (High Evidence).","entity_name":"LARS2","entity_type":"gene"},{"created":"2024-12-05T13:15:21.168711+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.299","user_name":"Chirag Patel","item_type":"entity","text":"gene: LARS2 was added\ngene: LARS2 was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: LARS2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: LARS2 were set to PMID: 32423379, 29205794, 23541342, 30737337, 26657938,\nPhenotypes for gene: LARS2 were set to Perrault syndrome 4; MIM# 615300\nReview for gene: LARS2 was set to GREEN\nAdded comment: Perrault syndrome-4 (PRLTS4) is an autosomal recessive disorder primarily characterized by early-onset sensorineural hearing loss in both males and females, and premature ovarian failure (POF) due to ovarian dysgenesis in females. Affected individuals may also develop neurologic involvement, including developmental delay or learning difficulties in childhood or onset of progressive movement abnormalities, such as spasticity, in adulthood. Brain imaging may show progressive leukodystrophy. At least 6 families with affected females reported with biallelic variants in LARS2 (mostly missense), which segregated in family. Patient-derived mitochondria showed decreased LARS2 aminoacylation activity (about 50% of controls) in one study. \nSources: Literature","entity_name":"LARS2","entity_type":"gene"},{"created":"2024-12-05T13:04:50.502843+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.298","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: ERAL1 as Amber List (moderate evidence)","entity_name":"ERAL1","entity_type":"gene"},{"created":"2024-12-05T13:04:50.451752+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.298","user_name":"Chirag Patel","item_type":"entity","text":"Gene: eral1 has been classified as Amber List (Moderate Evidence).","entity_name":"ERAL1","entity_type":"gene"},{"created":"2024-12-05T13:03:57.643109+11:00","panel_name":"Differences of Sex Development","panel_id":99,"panel_version":"0.297","user_name":"Chirag Patel","item_type":"entity","text":"reviewed gene: ERAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 28449065; Phenotypes: Perrault syndrome 6, MIM# 617565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ERAL1","entity_type":"gene"},{"created":"2024-12-04T17:18:46.852154+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.633","user_name":"Ee Ming Wong","item_type":"entity","text":"reviewed gene: MMAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblA type (MIM#251100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"MMAA","entity_type":"gene"},{"created":"2024-12-04T17:09:47.982586+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.633","user_name":"Ee Ming Wong","item_type":"entity","text":"reviewed gene: MERTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 11062461, 17301963, 20300561, 22180149; Phenotypes: Retinitis pigmentosa 38 (MIM#613862); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"MERTK","entity_type":"gene"},{"created":"2024-12-04T16:57:36.924692+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.633","user_name":"Ee Ming Wong","item_type":"entity","text":"reviewed gene: MARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 24103465, 25913036; Phenotypes: Interstitial lung and liver disease, MIM#615486; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"MARS","entity_type":"gene"},{"created":"2024-12-04T16:56:54.393322+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.633","user_name":"Cassandra Muller","item_type":"entity","text":"reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bartter syndrome, type 2, 241200 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"KCNJ1","entity_type":"gene"},{"created":"2024-12-04T16:48:59.763186+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.633","user_name":"Cassandra Muller","item_type":"entity","text":"reviewed gene: IKBKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 24369075, 25216719, 24679846, 32117824, 2513935; Phenotypes: Immunodeficiency 15, 615592 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"IKBKB","entity_type":"gene"},{"created":"2024-12-04T16:40:39.446541+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.633","user_name":"Cassandra Muller","item_type":"entity","text":"reviewed gene: HPS1: Rating: ; Mode of pathogenicity: None; Publications: 8896559, 9497254, 9705234, 27593200, 31898847; Phenotypes: Hermansky-Pudlak syndrome 1, 203300 (3); Mode of inheritance: None","entity_name":"HPS1","entity_type":"gene"},{"created":"2024-12-04T16:26:54.556543+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.633","user_name":"Cassandra Muller","item_type":"entity","text":"reviewed gene: HPD: Rating: AMBER; Mode of pathogenicity: None; Publications: 10942115, 23036342, 37817461, 28649543; Phenotypes: Tyrosinemia, type III, 276710 (3); Mode of inheritance: None","entity_name":"HPD","entity_type":"gene"},{"created":"2024-12-04T15:53:03.824229+11:00","panel_name":"Osteogenesis Imperfecta and Osteoporosis","panel_id":147,"panel_version":"0.115","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24088043; Phenotypes: X-linked osteoporosis with fractures MONDO:0018315; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)","entity_name":"PLS3","entity_type":"gene"},{"created":"2024-12-04T15:47:37.233469+11:00","panel_name":"Osteogenesis Imperfecta and Osteoporosis","panel_id":147,"panel_version":"0.115","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20034086; Phenotypes: osteoporosis-pseudoglioma syndrome MONDO:0009820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"LRP5","entity_type":"gene"},{"created":"2024-12-04T15:45:03.576855+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.633","user_name":"Cassandra Muller","item_type":"entity","text":"reviewed gene: HFE2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemochromatosis, type 2A, 602390 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"HFE2","entity_type":"gene"},{"created":"2024-12-04T15:39:03.008024+11:00","panel_name":"Osteogenesis Imperfecta and Osteoporosis","panel_id":147,"panel_version":"0.115","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: FKBP10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20362275, 20839288; Phenotypes: osteogenesis imperfecta type 11 MONDO:0012592, Bruck syndrome MONDO:0017195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"FKBP10","entity_type":"gene"},{"created":"2024-12-04T15:21:14.251506+11:00","panel_name":"Osteogenesis Imperfecta and Osteoporosis","panel_id":147,"panel_version":"0.115","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: COL1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301472, 2897363, 8257992, 8401517; Phenotypes: Osteogenesis imperfecta type 1 MONDO:0008146, Osteogenesis imperfecta type 2 MONDO:0008147, Osteogenesis imperfecta type 3 MONDO:0009804, Osteogenesis imperfecta type 4 MONDO:0008148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"COL1A2","entity_type":"gene"},{"created":"2024-12-04T15:18:09.616426+11:00","panel_name":"Osteogenesis Imperfecta and Osteoporosis","panel_id":147,"panel_version":"0.115","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"edited their review of gene: COL1A1: Changed publications: 20301472, 15728585, 17078022, 23692737","entity_name":"COL1A1","entity_type":"gene"},{"created":"2024-12-04T15:17:30.263365+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.633","user_name":"Cassandra Muller","item_type":"entity","text":"reviewed gene: GLYCTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 20949620, 31837836, 39619776; Phenotypes: D-glyceric aciduria, 220120 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"GLYCTK","entity_type":"gene"},{"created":"2024-12-04T15:17:02.265628+11:00","panel_name":"Osteogenesis Imperfecta and Osteoporosis","panel_id":147,"panel_version":"0.115","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15728585, 17078022, 23692737; Phenotypes: combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 MONDO:0030854, Osteogenesis imperfecta type 1 MONDO:0008146, Osteogenesis imperfecta type 2 MONDO:0008147, Osteogenesis imperfecta type 3 MONDO:0009804, Osteogenesis imperfecta type 4, MONDO:0008148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"COL1A1","entity_type":"gene"}]}