HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 220469,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=966",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=964",
"results": [
{
"created": "2022-02-28T10:33:54.191695+11:00",
"panel_name": "Atypical Haemolytic Uraemic Syndrome_MPGN",
"panel_id": 211,
"panel_version": "0.39",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: TSEN2 was added\ngene: TSEN2 was added to Atypical Haemolytic Uraemic Syndrome_MPGN. Sources: Literature\nMode of inheritance for gene: TSEN2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TSEN2 were set to PMID: 34964109\nPhenotypes for gene: TSEN2 were set to TRACK syndrome\nReview for gene: TSEN2 was set to GREEN\nAdded comment: Biallelic variants in TSEN2 cause pontocerebellar hypoplasia. Canpolat et a. (2022) report an intronic recessive founder variant in TSEN2 that results in abnormal splicing of the mRNA of this gene, in 6 individuals from 4 consanguineous families. Individuals were affected with microcephaly, craniofacial malformations, CNS abnormalities, cognitive retardation of variable severity, and all individuals developed atypical hemolytic uremic syndrome (aHUS) with thrombotic microangiopathy, microangiopathic hemolytic anemia, thrombocytopenia, proteinuria, severe hypertension, and end-stage kidney disease (ESKD) early in life. Bulk RNA sequencing of peripheral blood cells of 4 affected individuals revealed abnormal tRNA transcripts, indicating an alteration of the tRNA biogenesis. Morpholino-mediated skipping of exon 10 of tsen2 in zebrafish produced phenotypes similar to human patients. Proposed as TRACK syndrome (TSEN2 Related Atypical hemolytic uremic syndrome, Craniofacial malformations, Kidney failure). \nSources: Literature",
"entity_name": "TSEN2",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:28:28.215625+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.107",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: TSEN2 as Green List (high evidence)",
"entity_name": "TSEN2",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:28:28.203476+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.107",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: tsen2 has been classified as Green List (High Evidence).",
"entity_name": "TSEN2",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:28:18.124220+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4256",
"user_name": "Chloe Stutterd",
"item_type": "entity",
"text": "gene: D2HGDH was added\ngene: D2HGDH was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: D2HGDH was set to BIALLELIC, autosomal or pseudoautosomal\nReview for gene: D2HGDH was set to GREEN\nAdded comment: Antenatal features: macrocephaly, enlarged cerebral ventricles, micrognathia \nSources: Literature",
"entity_name": "D2HGDH",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:28:05.009764+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.107",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: TSEN2 as Green List (high evidence)",
"entity_name": "TSEN2",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:28:04.996521+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.107",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: tsen2 has been classified as Green List (High Evidence).",
"entity_name": "TSEN2",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:27:13.887902+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4256",
"user_name": "Chloe Stutterd",
"item_type": "entity",
"text": "gene: COLGALT1 was added\ngene: COLGALT1 was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal\nAdded comment: Antenatal features: porencephalic cyst, calcifications \nSources: Literature",
"entity_name": "COLGALT1",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:27:05.677946+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.106",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "reviewed gene: TSEN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None",
"entity_name": "TSEN2",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:25:54.007307+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4256",
"user_name": "Chloe Stutterd",
"item_type": "entity",
"text": "gene: C2orf69 was added\ngene: C2orf69 was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal\nReview for gene: C2orf69 was set to GREEN\nAdded comment: Antenatal features: microcephaly, thin CC, Dandy-Walker malformation \nSources: Literature",
"entity_name": "C2orf69",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:23:41.593398+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4256",
"user_name": "Chloe Stutterd",
"item_type": "entity",
"text": "gene: ABHD16A was added\ngene: ABHD16A was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal\nAdded comment: Antenatal features: thin CC, joint contractures/foot deformity \nSources: Literature",
"entity_name": "ABHD16A",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:13:20.658348+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4256",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: PPP2R3C as Green List (high evidence)",
"entity_name": "PPP2R3C",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:13:20.648392+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4256",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: ppp2r3c has been classified as Green List (High Evidence).",
"entity_name": "PPP2R3C",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:12:59.881141+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4255",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: PPP2R3C was added\ngene: PPP2R3C was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818\nPhenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419\nReview for gene: PPP2R3C was set to GREEN\nAdded comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility. \nSources: Literature",
"entity_name": "PPP2R3C",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:11:12.955119+11:00",
"panel_name": "Differences of Sex Development",
"panel_id": 99,
"panel_version": "0.241",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: PPP2R3C as Green List (high evidence)",
"entity_name": "PPP2R3C",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:11:12.944808+11:00",
"panel_name": "Differences of Sex Development",
"panel_id": 99,
"panel_version": "0.241",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: ppp2r3c has been classified as Green List (High Evidence).",
"entity_name": "PPP2R3C",
"entity_type": "gene"
},
{
"created": "2022-02-28T10:10:38.657763+11:00",
"panel_name": "Differences of Sex Development",
"panel_id": 99,
"panel_version": "0.240",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: PPP2R3C was added\ngene: PPP2R3C was added to Differences of Sex Development. Sources: Literature\nMode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818\nPhenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419\nReview for gene: PPP2R3C was set to GREEN\nAdded comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. \r\n\r\n11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility. \nSources: Literature",
"entity_name": "PPP2R3C",
"entity_type": "gene"
},
{
"created": "2022-02-28T09:55:15.460776+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4254",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: CDX2 as Green List (high evidence)",
"entity_name": "CDX2",
"entity_type": "gene"
},
{
"created": "2022-02-28T09:55:15.449312+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4254",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: cdx2 has been classified as Green List (High Evidence).",
"entity_name": "CDX2",
"entity_type": "gene"
},
{
"created": "2022-02-28T09:55:14.402711+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4254",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: CDX2 as Green List (high evidence)",
"entity_name": "CDX2",
"entity_type": "gene"
},
{
"created": "2022-02-28T09:55:14.391483+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4254",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: cdx2 has been classified as Green List (High Evidence).",
"entity_name": "CDX2",
"entity_type": "gene"
},
{
"created": "2022-02-28T09:54:48.310650+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4253",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "reviewed gene: CDX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29177441, 34671974; Phenotypes: Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "CDX2",
"entity_type": "gene"
},
{
"created": "2022-02-28T09:54:13.176315+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.11072",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: CDX2 as Green List (high evidence)",
"entity_name": "CDX2",
"entity_type": "gene"
},
{
"created": "2022-02-28T09:54:13.164240+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.11072",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: cdx2 has been classified as Green List (High Evidence).",
"entity_name": "CDX2",
"entity_type": "gene"
},
{
"created": "2022-02-28T09:53:54.697275+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.11071",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "edited their review of gene: CDX2: Added comment: 9 families, with heterozygous variants identified with WES, presenting with congenital abnormalities affecting the development of the anus, the renal and urogenital system, the vertebrae and/or the limbs in varying sequences and severity (incl. sirenomelia and persistent cloaca). A recurrent pathogenic missense variant in the HOX domain of the protein p.(Arg237His) was found in 3 unrelated families. In the mouse cdx2 is essential for anteroposterior patterning of embryonal axis and morphogenesis of cloacal structures. Cdx2 heterozygous conditional mutant mice show a variable phenotype (including imperforate anus, sirenomelia, posterior vertebral truncations, and bladder anomalies).; Changed rating: GREEN; Changed publications: PMID: 29177441, 34671974; Changed phenotypes: Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs; Set current diagnostic: yes",
"entity_name": "CDX2",
"entity_type": "gene"
},
{
"created": "2022-02-26T01:36:22.639263+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.106",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: CHKA was added\ngene: CHKA was added to Microcephaly. Sources: Literature\nMode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CHKA were set to 35202461\nPhenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature\nPenetrance for gene: CHKA were set to Complete\nReview for gene: CHKA was set to GREEN\nAdded comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants. \r\n\r\nShared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.\r\n\r\nEventual previous genetic testing was not discussed.\r\n\r\nExome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.\r\n\r\nOther variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.\r\n\r\n3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2): \r\n- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],\r\n- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents], \r\n- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],\r\n- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.\r\n\r\nCHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.\r\n\r\nCHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.\r\n\r\nAs the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].\r\n\r\nOther disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.\r\n\r\nCHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.\r\n\r\nIn silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).\r\n\r\nEach of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).\r\n\r\nNMD is thought to underly the deleterious effect of the frameshift one (not studied).\r\n\r\nThe start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein. \r\n\r\nChka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).\r\n\r\nThere is no associated phenotype in OMIM, Gene2Phenotype or SysID.\r\n\r\nOverall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset). \nSources: Literature",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-02-26T01:36:08.953970+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1451",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: CHKA was added\ngene: CHKA was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CHKA were set to 35202461\nPhenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature\nPenetrance for gene: CHKA were set to Complete\nReview for gene: CHKA was set to GREEN\nAdded comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants. \r\n\r\nShared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.\r\n\r\nEventual previous genetic testing was not discussed.\r\n\r\nExome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.\r\n\r\nOther variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.\r\n\r\n3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2): \r\n- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],\r\n- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents], \r\n- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],\r\n- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.\r\n\r\nCHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.\r\n\r\nCHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.\r\n\r\nAs the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].\r\n\r\nOther disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.\r\n\r\nCHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.\r\n\r\nIn silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).\r\n\r\nEach of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).\r\n\r\nNMD is thought to underly the deleterious effect of the frameshift one (not studied).\r\n\r\nThe start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein. \r\n\r\nChka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).\r\n\r\nThere is no associated phenotype in OMIM, Gene2Phenotype or SysID.\r\n\r\nOverall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset). \nSources: Literature",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-02-26T01:35:59.524435+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4507",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: CHKA was added\ngene: CHKA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CHKA were set to 35202461\nPhenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature\nPenetrance for gene: CHKA were set to Complete\nReview for gene: CHKA was set to GREEN\nAdded comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants. \r\n\r\nShared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.\r\n\r\nEventual previous genetic testing was not discussed.\r\n\r\nExome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.\r\n\r\nOther variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.\r\n\r\n3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2): \r\n- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],\r\n- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents], \r\n- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],\r\n- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.\r\n\r\nCHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.\r\n\r\nCHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.\r\n\r\nAs the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].\r\n\r\nOther disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.\r\n\r\nCHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.\r\n\r\nIn silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).\r\n\r\nEach of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).\r\n\r\nNMD is thought to underly the deleterious effect of the frameshift one (not studied).\r\n\r\nThe start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein. \r\n\r\nChka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).\r\n\r\nThere is no associated phenotype in OMIM, Gene2Phenotype or SysID.\r\n\r\nOverall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset). \nSources: Literature",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-02-26T01:35:43.443962+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.11071",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: CHKA was added\ngene: CHKA was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CHKA were set to 35202461\nPhenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature\nPenetrance for gene: CHKA were set to Complete\nReview for gene: CHKA was set to GREEN\nAdded comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants. \r\n\r\nShared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.\r\n\r\nEventual previous genetic testing was not discussed.\r\n\r\nExome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.\r\n\r\nOther variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.\r\n\r\n3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2): \r\n- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],\r\n- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents], \r\n- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],\r\n- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.\r\n\r\nCHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.\r\n\r\nCHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.\r\n\r\nAs the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].\r\n\r\nOther disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.\r\n\r\nCHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.\r\n\r\nIn silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).\r\n\r\nEach of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).\r\n\r\nNMD is thought to underly the deleterious effect of the frameshift one (not studied).\r\n\r\nThe start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein. \r\n\r\nChka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).\r\n\r\nThere is no associated phenotype in OMIM, Gene2Phenotype or SysID.\r\n\r\nOverall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset). \nSources: Literature",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-02-25T17:33:10.218918+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4253",
"user_name": "Belinda Chong",
"item_type": "entity",
"text": "gene: UNC13A was added\ngene: UNC13A was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: UNC13A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: UNC13A were set to 27648472; 28192369\nPhenotypes for gene: UNC13A were set to Congenital myasthenia; dyskinesia; autism; developmental delay\nReview for gene: UNC13A was set to RED\nAdded comment: One individual described with biallelic variants in this gene and a myasthenic syndrome; another individual reported with de novo variant in this gene and a different neurological phenotype (abnormal movements, developmental delay and autism). \nSources: Literature",
"entity_name": "UNC13A",
"entity_type": "gene"
},
{
"created": "2022-02-25T17:16:34.365862+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4253",
"user_name": "Belinda Chong",
"item_type": "entity",
"text": "gene: SYT2 was added\ngene: SYT2 was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: SYT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: SYT2 were set to 25192047; 32776697; 32250532; 30533528\nPhenotypes for gene: SYT2 were set to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461\nReview for gene: SYT2 was set to GREEN\ngene: SYT2 was marked as current diagnostic\nAdded comment: Myasthenic syndrome bi-allelic #619461- Decreased fetal movements\r\n\r\nMono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in three families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.\r\n\r\nBi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function. \nSources: Literature",
"entity_name": "SYT2",
"entity_type": "gene"
},
{
"created": "2022-02-25T17:00:11.129469+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4253",
"user_name": "Belinda Chong",
"item_type": "entity",
"text": "gene: SLC25A1 was added\ngene: SLC25A1 was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: SLC25A1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC25A1 were set to 26870663; 31527857; 29226520\nPhenotypes for gene: SLC25A1 were set to ?Myasthenic syndrome, congenital, 23, presynaptic MIM#618197; Combined D-2- and L-2-hydroxyglutaric aciduria MIM#615182\nReview for gene: SLC25A1 was set to RED\ngene: SLC25A1 was marked as current diagnostic\nAdded comment: Neonatal onset.\r\n\r\nGreen for MIM#618197\r\nFour unrelated families. mild congenital myasthenic syndrome.\r\n\r\nRed for MIM#615182\r\nFive infants of two consanguineous Bedouin families of the same tribe homozygous for the same variant with EEG compatible with white matter disorder. Death usually occurs in childhood. \nSources: Literature",
"entity_name": "SLC25A1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:32:47.489631+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4253",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NHS as ready",
"entity_name": "NHS",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:32:47.478583+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4253",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: nhs has been classified as Green List (High Evidence).",
"entity_name": "NHS",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:32:44.177294+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4253",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NHS were changed from CATARACT CONGENITAL X-LINKED; NANCE-HORAN SYNDROME to Nance-Horan syndrome, MIM# 302350",
"entity_name": "NHS",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:32:23.850867+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4252",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Mode of inheritance for gene: NHS was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)",
"entity_name": "NHS",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:30:30.258512+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4251",
"user_name": "Belinda Chong",
"item_type": "entity",
"text": "gene: RPH3A was added\ngene: RPH3A was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: RPH3A was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: RPH3A were set to 29441694\nPhenotypes for gene: RPH3A were set to Congenital myasthenic syndrome\nReview for gene: RPH3A was set to RED\ngene: RPH3A was marked as current diagnostic\nAdded comment: Only one patient with a complex phenotype that included myasthenia, with compound het missense variants, of which only one variant had plausible functional expression data. \nSources: Literature",
"entity_name": "RPH3A",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:27:17.907008+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4251",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NHEJ1 as ready",
"entity_name": "NHEJ1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:27:17.896116+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4251",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: nhej1 has been classified as Green List (High Evidence).",
"entity_name": "NHEJ1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:27:09.579791+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4251",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Cernunnos-XLF deficiency MONDO:0012650",
"entity_name": "NHEJ1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:26:40.414716+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4250",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Publications for gene: NHEJ1 were set to ",
"entity_name": "NHEJ1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:26:08.236629+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4249",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30898087, 30666249, 28741180, 25288157, 24511403, 21721379, 21535335; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291, Cernunnos-XLF deficiency MONDO:0012650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "NHEJ1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:22:51.612538+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4249",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NF1 as ready",
"entity_name": "NF1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:22:51.600343+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4249",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: nf1 has been classified as Green List (High Evidence).",
"entity_name": "NF1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:22:22.315816+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4249",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurofibromatosis, type 1, MIM# 162200, Neurofibromatosis-Noonan syndrome, MIM# 601321; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "NF1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:20:28.639395+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4249",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NF1 were changed from FAMILIAL SPINAL NEUROFIBROMATOSIS; NEUROFIBROMATOSIS-NOONAN SYNDROME; WATSON SYNDROME; NEUROFIBROMATOSIS TYPE 1 to Neurofibromatosis, type 1, MIM# 162200; Neurofibromatosis-Noonan syndrome, MIM# 601321",
"entity_name": "NF1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:20:02.661434+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4248",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Mode of inheritance for gene: NF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "NF1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:09:00.377675+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4247",
"user_name": "Belinda Chong",
"item_type": "entity",
"text": "gene: PLEC was added\ngene: PLEC was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: PLEC was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: PLEC were set to 22144912; 31509265; 21263134; 20624679; 20624679; 21109228; 28824526\nPhenotypes for gene: PLEC were set to Epidermolysis bullosa simplex 5C, with pyloric atresia\tMIM#612138; Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex 5A, Ogna type\tMIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17 (MIM#613723)\nReview for gene: PLEC was set to GREEN\ngene: PLEC was marked as current diagnostic\nAdded comment: Multiple variations of EB and also associated with limb-girdle muscular dystrophy. Neonatal to Early childhood onset. However, Epidermolysis bullosa simplex 5C, with pyloric atresia\tMIM#612138 has prenatal manifestation of Polyhydramnios. \nSources: Literature",
"entity_name": "PLEC",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:06:59.692076+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4247",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NEK1 as ready",
"entity_name": "NEK1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:06:59.680075+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4247",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: nek1 has been classified as Green List (High Evidence).",
"entity_name": "NEK1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:06:54.431148+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4247",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NEK1 were changed from SHORT RIB-POLYDACTYLY SYNDROME, TYPE II; Short-rib thoracic dysplasia 6 with or without polydactyly, 263520; SHORT RIB-POLYDACTYLY SYNDORME, TYPE II to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520",
"entity_name": "NEK1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:06:31.789860+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4246",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Publications for gene: NEK1 were set to ",
"entity_name": "NEK1",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:05:22.623759+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4245",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NEB as ready",
"entity_name": "NEB",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:05:22.611957+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4245",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: neb has been classified as Green List (High Evidence).",
"entity_name": "NEB",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:05:18.992012+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4245",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NEB were changed from AUTOSOMAL RECESSIVE TYPICAL NEMALINE MYOPATHY to Arthrogryposis multiplex congenita 6, MIM# 619334",
"entity_name": "NEB",
"entity_type": "gene"
},
{
"created": "2022-02-25T16:05:05.209460+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4244",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Publications for gene: NEB were set to ",
"entity_name": "NEB",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:51:33.065405+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4243",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NDUFAF5 as ready",
"entity_name": "NDUFAF5",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:51:33.055476+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4243",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: ndufaf5 has been classified as Green List (High Evidence).",
"entity_name": "NDUFAF5",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:51:26.194015+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4243",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NDUFAF5 were changed from Mitochondrial complex I deficiency, nuclear type 16, 618238 to Mitochondrial complex I deficiency, nuclear type 16, MIM# 618238",
"entity_name": "NDUFAF5",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:51:07.654913+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4242",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Publications for gene: NDUFAF5 were set to 30266093; 18940309; 21620786",
"entity_name": "NDUFAF5",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:50:21.215120+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4241",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "reviewed gene: NDUFAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 16, MIM# 618238; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "NDUFAF5",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:46:30.982201+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4241",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NDP as ready",
"entity_name": "NDP",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:46:30.972677+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4241",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: ndp has been classified as Green List (High Evidence).",
"entity_name": "NDP",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:46:01.796590+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4241",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Norrie disease, MIM# 310600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females",
"entity_name": "NDP",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:45:01.725342+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4241",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NDP were changed from NORRIE DISEASE to Norrie disease, MIM# 310600",
"entity_name": "NDP",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:43:10.020286+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4240",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NDE1 as ready",
"entity_name": "NDE1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:43:09.991267+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4240",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: nde1 has been classified as Green List (High Evidence).",
"entity_name": "NDE1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:42:59.239458+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4240",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NDE1 were changed from LISSENCEPHALY 4 to Lissencephaly 4 (with microcephaly), MIM# 614019; MONDO:0013527; Microhydranencephaly, MIM# 605013; MONDO:0011504",
"entity_name": "NDE1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:42:38.088484+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4239",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Publications for gene: NDE1 were set to ",
"entity_name": "NDE1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:41:07.815393+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4238",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Publications for gene: NBN were set to ",
"entity_name": "NBN",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:40:35.363370+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4237",
"user_name": "Belinda Chong",
"item_type": "entity",
"text": "gene: LAMA5 was added\ngene: LAMA5 was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: LAMA5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: LAMA5 were set to 33242826; 29534211; 16790509; 30589377; 28735299; 30631761\nPhenotypes for gene: LAMA5 were set to bent bone dysplasia; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay\nReview for gene: LAMA5 was set to RED\nAdded comment: Currently amber gene and appears postnatal onset (not enough information) \r\n\r\nPMID: 29534211 - Three consanguineous families with homozygous missense variants (VUS) identified in two affected siblings with paediatric nephrotic syndrome within each family. No functional studies conducted on the missense variants.\r\nPMID: 16790509 - A hypomorphic Lama5 homozygous mouse model demonstrated proteinuria, cystic kidney disease and death from progressive renal failure at 3–4 weeks of age.\r\nPMID: 24130771 - a single case focal segmental glomerulosclerosis (proteinuria) with biallelic missense variants (VUS - S1469A & V2440I). Also reports p.Gly3685Arg in 2 other cases, which has 11 homozygotes in gnomAD v2.1\r\nPMID: 29764427, 30808327 - Four families with haematuria and proteinuria reported with digenic inheritance of a LAMA5 missense variant with a COL4A4/5 variant. One of those variants (p.His1717Tyr) has 892 homozygotes in gnomAD v2.1\r\nPMID: 28735299, 30589377 - A single large multigenerational family with a multisystem syndrome (including ophthalmic fetures), segregating a heterozygous missense p.V3140M, and supporting knock-in mouse model that recapitulates the phenotype.\r\nPMID: 33242826 - A single family with a bent bone dysplasia in 3 affected siblings with biallelic variants, and some supporting in vitro functional assays.\r\nPMID: 28544784, 29377152 - Single family with congenital myasthenic syndrome with a homozygous missense reported twice.\r\nPMID: 30631761 - a single case with a de novo splice site variant with developmental delay, epilepsy, and hypotonia \nSources: Literature",
"entity_name": "LAMA5",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:24:09.106941+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4237",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NBN as ready",
"entity_name": "NBN",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:24:09.093356+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4237",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: nbn has been classified as Green List (High Evidence).",
"entity_name": "NBN",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:24:04.906645+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4237",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NBN were changed from NIJMEGEN BREAKAGE SYNDROME to Nijmegen breakage syndrome, MIM# 251260",
"entity_name": "NBN",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:23:32.399757+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4236",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "reviewed gene: NBN: Rating: GREEN; Mode of pathogenicity: None; Publications: 7545870, 2421804, 8914736, 3802554; Phenotypes: Nijmegen breakage syndrome, MIM#251260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "NBN",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:20:54.768955+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4236",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Classified gene: NBN as Green List (high evidence)",
"entity_name": "NBN",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:20:54.758633+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4236",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: nbn has been classified as Green List (High Evidence).",
"entity_name": "NBN",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:17:33.222135+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4235",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: NACC1 as ready",
"entity_name": "NACC1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:17:33.211596+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4235",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: nacc1 has been classified as Green List (High Evidence).",
"entity_name": "NACC1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:17:28.894541+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4235",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Added comment: Comment on phenotypes: Fetal anomalies reported include cataracts (5/7 patients) and microcephaly (5/7) patients",
"entity_name": "NACC1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:17:28.866587+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4235",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: NACC1 were changed from Infantile Epilepsy, Cataracts, and Profound Developmental Delay to Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination delayed brain myelination, MIM# 617393)",
"entity_name": "NACC1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:15:44.680519+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4234",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Publications for gene: NACC1 were set to ",
"entity_name": "NACC1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:15:20.649826+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4233",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Mode of inheritance for gene: NACC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "NACC1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:13:05.973931+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4232",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: MYT1 as ready",
"entity_name": "MYT1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:13:05.962955+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4232",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: myt1 has been classified as Green List (High Evidence).",
"entity_name": "MYT1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:12:58.309310+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4232",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: MYT1 were changed from Oculo-auriculo-vertebral spectrum (OAVS); OAVS/Goldenhar syndrome to Hemifacial microsomia, MONDO:0015398",
"entity_name": "MYT1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:10:20.849668+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4231",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Publications for gene: MYT1 were set to 28612832; 27358179",
"entity_name": "MYT1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:09:57.781230+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4230",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Mode of inheritance for gene: MYT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "MYT1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:09:35.803422+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4229",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "changed review comment from: Associated with OAV spectrum / hemifacial microsomia; to: Reported in patients with OAV spectrum / hemifacial microsomia",
"entity_name": "MYT1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:09:05.102422+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4229",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "reviewed gene: MYT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28612832, 32871052, 27358179; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "MYT1",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:04:03.941211+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4229",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Marked gene: MYRF as ready",
"entity_name": "MYRF",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:04:03.931870+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4229",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Gene: myrf has been classified as Green List (High Evidence).",
"entity_name": "MYRF",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:03:52.749510+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4229",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Phenotypes for gene: MYRF were changed from Congenital diaphragmatic hernia (CDH); Cardiac-urogenital syndrome, 618280; Disorders of sex development (DSD) to Cardiac-urogenital syndrome, MIM# 618280",
"entity_name": "MYRF",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:03:24.230877+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4228",
"user_name": "Alison Yeung",
"item_type": "entity",
"text": "Mode of inheritance for gene: MYRF was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "MYRF",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:00:48.744077+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4227",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SNRPB as ready",
"entity_name": "SNRPB",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:00:48.730243+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4227",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: snrpb has been classified as Green List (High Evidence).",
"entity_name": "SNRPB",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:00:44.257191+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4227",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: SNRPB were changed from CEREBRO-COSTO-MANDIBULAR SYNDROME to Cerebrocostomandibular syndrome, MIM# 117650",
"entity_name": "SNRPB",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:00:26.462393+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4226",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: SNRPB were set to ",
"entity_name": "SNRPB",
"entity_type": "gene"
},
{
"created": "2022-02-25T15:00:11.416393+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4225",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: SNRPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "SNRPB",
"entity_type": "gene"
},
{
"created": "2022-02-25T14:58:41.701968+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4224",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SON as ready",
"entity_name": "SON",
"entity_type": "gene"
},
{
"created": "2022-02-25T14:58:41.691008+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4224",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: son has been classified as Green List (High Evidence).",
"entity_name": "SON",
"entity_type": "gene"
}
]
}