{"count":221304,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1189","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1187","results":[{"created":"2021-10-11T14:59:09.666425+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1280","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CLPB as ready","entity_name":"CLPB","entity_type":"gene"},{"created":"2021-10-11T14:59:09.656177+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1280","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: clpb has been classified as Green List (High Evidence).","entity_name":"CLPB","entity_type":"gene"},{"created":"2021-10-11T14:59:02.322085+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1280","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: CLPB as Green List (high evidence)","entity_name":"CLPB","entity_type":"gene"},{"created":"2021-10-11T14:59:02.311036+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1280","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: clpb has been classified as Green List (High Evidence).","entity_name":"CLPB","entity_type":"gene"},{"created":"2021-10-11T14:58:21.554479+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1279","user_name":"Zornitza Stark","item_type":"entity","text":"gene: CLPB was added\ngene: CLPB was added to Genetic Epilepsy. Sources: Expert Review\nMode of inheritance for gene: CLPB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: CLPB were set to 25597510; 34140661\nPhenotypes for gene: CLPB were set to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271\nReview for gene: CLPB was set to GREEN\nAdded comment: Bi-allelic variants: 3-Methylglutaconic aciduria (MGCA7) is an autosomal recessive inborn error of metabolism characterized primarily by increased levels of 3-methylglutaconic acid (3-MGA) associated with neurologic deterioration and neutropenia. The phenotype is highly variable: most patients have infantile onset of a progressive encephalopathy with various movement abnormalities and delayed psychomotor development, although rare patients with normal neurologic development have been reported. Other common, but variable, features include cataracts, seizures, and recurrent infections. More than 10 unrelated families reported.\r\n\r\nMono-allelic variants: six unrelated individuals reported with de novo variants and neutropaenia, epilepsy, developmental issues, and 3-methylglutaconic aciduria. \nSources: Expert Review","entity_name":"CLPB","entity_type":"gene"},{"created":"2021-10-11T14:52:02.107710+11:00","panel_name":"Short QT syndrome","panel_id":174,"panel_version":"0.1","user_name":"Daniel Flanagan","item_type":"entity","text":"gene: SLC4A3 was added\ngene: SLC4A3 was added to Short QT syndrome. Sources: Expert Review\nMode of inheritance for gene: SLC4A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: SLC4A3 were set to PMID: 29167417; 34557911\nPhenotypes for gene: SLC4A3 were set to Short QT syndrome\nReview for gene: SLC4A3 was set to GREEN\nAdded comment: Moderate evidence for autosomal dominant short QT syndrome 1 by ClinGen /gene curation expert panel (PMID: 34557911). A single missense variant (absent gnomAD) identified in two SQTS families. In family 1, it segregated with SQTS (QTc<370ms) in 23 carriers, and 19 non-carriers had a QTc>370ms.  In family 2, it segregated in 4 individuals. Experimental evidence from in vitro and zebrafish models suggests reduced membrane localization of the mutated protein leads to intracellular alkalinization and shortening of the cardiomyocyte action potential duration. \r\nClinGen expert panel was divided between strong (4 votes) and moderate (5 votes). \nSources: Expert Review","entity_name":"SLC4A3","entity_type":"gene"},{"created":"2021-10-11T14:51:08.175834+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1278","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CLN6 as ready","entity_name":"CLN6","entity_type":"gene"},{"created":"2021-10-11T14:51:08.163449+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1278","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: cln6 has been classified as Green List (High Evidence).","entity_name":"CLN6","entity_type":"gene"},{"created":"2021-10-11T14:50:59.632432+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1278","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: CLN6 as Green List (high evidence)","entity_name":"CLN6","entity_type":"gene"},{"created":"2021-10-11T14:50:59.621561+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1278","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: cln6 has been classified as Green List (High Evidence).","entity_name":"CLN6","entity_type":"gene"},{"created":"2021-10-11T14:48:40.237743+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1277","user_name":"Zornitza Stark","item_type":"entity","text":"gene: CLN6 was added\ngene: CLN6 was added to Genetic Epilepsy. Sources: Expert Review\nMode of inheritance for gene: CLN6 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CLN6 were set to 11791207; 11727201; 21549341; 33798445; 33024953\nPhenotypes for gene: CLN6 were set to Ceroid lipofuscinosis, neuronal, 6, MIM# 601780; Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, MIM# 204300\nReview for gene: CLN6 was set to GREEN\nAdded comment: Well established gene-disease association, seizures are part of the phenotype. \nSources: Expert Review","entity_name":"CLN6","entity_type":"gene"},{"created":"2021-10-11T13:45:43.805162+11:00","panel_name":"Short QT syndrome","panel_id":174,"panel_version":"0.1","user_name":"Daniel Flanagan","item_type":"entity","text":"reviewed gene: KCNJ2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34557911; Phenotypes: Short QT syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes","entity_name":"KCNJ2","entity_type":"gene"},{"created":"2021-10-11T13:32:51.744477+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Ain Roesley","item_type":"entity","text":"gene: PNPT1 was added\ngene: PNPT1 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: PNPT1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PNPT1 were set to 33158637; 31752325\nPenetrance for gene: PNPT1 were set to unknown\nReview for gene: PNPT1 was set to GREEN\nAdded comment: PMID:33158637\r\n1x homozygous (c.1399C > T, p.Pro467Ser) in an individual who presented with a phenotype similar to Aicardi-Goutieres Syndrome. She presented with feeding difficulties and vomiting, muscle weakness, and hyperexcitability, accompanied by a sterile febrile episode. Later developed refractory focal impaired awareness and pharmaco-refractory generalized seizures.\r\n\r\nPMID: 31752325\r\n7 presented with seizures (out of 21 for whom clinical info was available) \nSources: Literature","entity_name":"PNPT1","entity_type":"gene"},{"created":"2021-10-11T13:31:21.200029+11:00","panel_name":"Short QT syndrome","panel_id":174,"panel_version":"0.1","user_name":"Daniel Flanagan","item_type":"entity","text":"changed review comment from: Strong evidence for autosomal dominant short QT syndrome by ClinGen and gene curation expert panel (PMID: 34557911). 9 SQTS probands reported, eight of which had the p.(Val141Met) variant. All 9 probands presented with severe bradycardia in-utero or at birth and in 6 atrial fibrillation. Reviewed as strong because most of the evidence is related to a single variant.; to: Strong evidence for autosomal dominant short QT syndrome by ClinGen and gene curation expert panel (PMID: 34557911). 9 SQTS probands reported, eight of which had the p.(Val141Met) variant. All 9 probands presented with severe bradycardia in-utero or at birth and in 6 atrial fibrillation. Reviewed as strong because most of the evidence is related to a single variant.\r\nGain of function mechanism reported.","entity_name":"KCNQ1","entity_type":"gene"},{"created":"2021-10-11T13:24:54.058134+11:00","panel_name":"Short QT syndrome","panel_id":174,"panel_version":"0.1","user_name":"Daniel Flanagan","item_type":"entity","text":"reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34557911; Phenotypes: Short QT syndrome 1, bradycardia, atrial fibrillation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes","entity_name":"KCNQ1","entity_type":"gene"},{"created":"2021-10-11T13:09:39.100114+11:00","panel_name":"Short QT syndrome","panel_id":174,"panel_version":"0.1","user_name":"Daniel Flanagan","item_type":"entity","text":"reviewed gene: KCNH2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34557911; Phenotypes: Short QT syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes","entity_name":"KCNH2","entity_type":"gene"},{"created":"2021-10-11T13:07:40.730484+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Ain Roesley","item_type":"entity","text":"gene: PHF6 was added\ngene: PHF6 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: PHF6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPublications for gene: PHF6 were set to 32399860\nPhenotypes for gene: PHF6 were set to Borjeson-Forssman-Lehmann syndrome\tMIM#301900\nPenetrance for gene: PHF6 were set to unknown\nReview for gene: PHF6 was set to GREEN\nAdded comment: Epilepsy is part of the phenotypic spectrum for Borjeson-Forssman-Lehmann syndrome (OMIM). At least 18 mutations known to date. \nSources: Literature","entity_name":"PHF6","entity_type":"gene"},{"created":"2021-10-11T12:51:07.378290+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Ain Roesley","item_type":"entity","text":"gene: PGM3 was added\ngene: PGM3 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: PGM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: PGM3 were set to 33193641\nPhenotypes for gene: PGM3 were set to Idiopathic focal epilepsy\nPenetrance for gene: PGM3 were set to Incomplete\nReview for gene: PGM3 was set to AMBER\nAdded comment: 4x unrelated families including 2x de novo +2x inherited from unaffected parents. Hence reduced penetrance suggested\r\n3x missense, 1x protein truncating\r\nboth missense variants inherited from unaffected parents classified as VUS by ACMG guidelines\r\n\r\nno functional studies done \nSources: Literature","entity_name":"PGM3","entity_type":"gene"},{"created":"2021-10-11T12:28:33.833647+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Krithika Murali","item_type":"entity","text":"gene: TARS2 was added\ngene: TARS2 was added to Genetic Epilepsy. Sources: Expert list,Literature\nMode of inheritance for gene: TARS2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TARS2 were set to 33153448; 24827421; 34508595\nPhenotypes for gene: TARS2 were set to Combined oxidative phosphorylation deficiency 21 - 615918; Epilepsy\nReview for gene: TARS2 was set to GREEN\nAdded comment: 8 cases from 7 unrelated families are reported in the literature with early-onset mitochondrial encephalomyopathy and a broad phenotypic spectrum that includes epilepsy. \nSources: Expert list, Literature","entity_name":"TARS2","entity_type":"gene"},{"created":"2021-10-11T11:53:35.321944+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Krithika Murali","item_type":"entity","text":"gene: TBX19 was added\ngene: TBX19 was added to Genetic Epilepsy. Sources: Expert list,Literature\nMode of inheritance for gene: TBX19 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TBX19 were set to 31998673\nPhenotypes for gene: TBX19 were set to Adrenocorticotropic hormone deficiency - 201400\nReview for gene: TBX19 was set to GREEN\nAdded comment: Well-established gene-disease association with congenital isolated ACTH deficiency.  Affected individuals can present with seizures in conjunction with hypoglycaemia and cholestasis.\r\n\r\nAlthough this gene is not associated with primary epilepsy and is a primary pituitary disorder, early detection and prompt institution of glucocorticoid treatment is vital to lower the risk of recurrent hypoglycemia and uncontrolled epilepsy.  As patients can present with seizures, inclusion in this panel may aid timely diagnosis of this rare but treatable disorder. \nSources: Expert list, Literature","entity_name":"TBX19","entity_type":"gene"},{"created":"2021-10-11T11:26:48.850339+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Krithika Murali","item_type":"entity","text":"gene: THG1L was added\ngene: THG1L was added to Genetic Epilepsy. Sources: Expert list,Literature\nMode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: THG1L were set to 33682303\nPhenotypes for gene: THG1L were set to Spinocerebellar ataxia, autosomal recessive 28 - 618800; Epilepsy\nReview for gene: THG1L was set to AMBER\nAdded comment: 3 individuals from 2 unrelated families of Ashkenazi Jewish descent with compound heterozygous variants ( p.Cys51Trp and p.Val55Ala) presented with profound developmental delays, microcephaly, intractable epilepsy, and cerebellar hypoplasia. \nSources: Expert list, Literature","entity_name":"THG1L","entity_type":"gene"},{"created":"2021-10-11T11:02:53.362556+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Krithika Murali","item_type":"entity","text":"reviewed gene: TRAPPC12: Rating: AMBER; Mode of pathogenicity: None; Publications: 28777934, 32369837; Phenotypes: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity - 617669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"TRAPPC12","entity_type":"gene"},{"created":"2021-10-11T10:06:17.714763+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Krithika Murali","item_type":"entity","text":"gene: TRPC3 was added\ngene: TRPC3 was added to Genetic Epilepsy. Sources: Expert list,Literature\nMode of inheritance for gene: TRPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: TRPC3 were set to 32135163; 25477146\nPhenotypes for gene: TRPC3 were set to ?Spinocerebellar ataxia 41 - 616410\nReview for gene: TRPC3 was set to RED\nAdded comment: Postulated association with adult-onset cerebellar ataxia based on one case with potentially pathogenic variant (Fogel et al Mov Disorder 2015)\r\n\r\nLiang et al 2020 Neurosci Letter observed elevated TRPC3 protein expression in focal cortical dysplasia tissue specimens compared with controls. \r\n\r\nNo formal gene-disease association with epilepsy has been reported. \nSources: Expert list, Literature","entity_name":"TRPC3","entity_type":"gene"},{"created":"2021-10-08T18:38:23.223978+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MAPK8IP3 as ready","entity_name":"MAPK8IP3","entity_type":"gene"},{"created":"2021-10-08T18:38:23.214475+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).","entity_name":"MAPK8IP3","entity_type":"gene"},{"created":"2021-10-08T18:38:10.341128+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MAPK8IP3 as Amber List (moderate evidence)","entity_name":"MAPK8IP3","entity_type":"gene"},{"created":"2021-10-08T18:38:10.327724+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1276","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).","entity_name":"MAPK8IP3","entity_type":"gene"},{"created":"2021-10-08T16:57:49.677738+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1275","user_name":"Elena Savva","item_type":"entity","text":"gene: MAPK8IP3 was added\ngene: MAPK8IP3 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: MAPK8IP3 were set to PMID: 30612693\nPhenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities MIM#618443\nReview for gene: MAPK8IP3 was set to AMBER\nAdded comment: 5/13 patients had generalized seizures, but for 3/13 it was a single event, 1/13 it was recurrent. All individuals had missense variants. \nSources: Literature","entity_name":"MAPK8IP3","entity_type":"gene"},{"created":"2021-10-08T16:03:02.179209+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.31","user_name":"Bryony Thompson","item_type":"entity","text":"Publications for gene: KL were set to 18308935","entity_name":"KL","entity_type":"gene"},{"created":"2021-10-08T16:01:41.791301+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.30","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: KL as Amber List (moderate evidence)","entity_name":"KL","entity_type":"gene"},{"created":"2021-10-08T16:01:41.780680+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.30","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: kl has been classified as Amber List (Moderate Evidence).","entity_name":"KL","entity_type":"gene"},{"created":"2021-10-08T16:01:12.186449+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.29","user_name":"Bryony Thompson","item_type":"entity","text":"edited their review of gene: KL: Added comment: 1 case reported with tumoral calcinosis and a homozygous missense, and 1 adult case reported with chronic kidney disease and hyperphosphatemia and a heterozygous frameshift variant. Also, supporting null mouse model.; Changed rating: AMBER; Changed publications: 18308935, 17710231, 31013726, 9363890; Changed phenotypes: Hypophosphatemic rickets, hyperparathyroidism, Tumoral calcinosis, hyperphosphatemic, familial, 3 MIM#617994, Hyperphosphatemia; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"KL","entity_type":"gene"},{"created":"2021-10-08T15:37:27.852589+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.28","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: CTNS as ready","entity_name":"CTNS","entity_type":"gene"},{"created":"2021-10-08T15:37:27.834293+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.28","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: ctns has been classified as Green List (High Evidence).","entity_name":"CTNS","entity_type":"gene"},{"created":"2021-10-08T15:36:10.959261+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.28","user_name":"Bryony Thompson","item_type":"entity","text":"Classified gene: CTNS as Green List (high evidence)","entity_name":"CTNS","entity_type":"gene"},{"created":"2021-10-08T15:36:10.942325+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.28","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: ctns has been classified as Green List (High Evidence).","entity_name":"CTNS","entity_type":"gene"},{"created":"2021-10-08T15:35:41.281778+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.27","user_name":"Bryony Thompson","item_type":"entity","text":"gene: CTNS was added\ngene: CTNS was added to Hypophosphataemic Rickets. Sources: Expert list\nMode of inheritance for gene: CTNS was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CTNS were set to 20301574; 9537412; 31068690\nPhenotypes for gene: CTNS were set to Cystinosis, nephropathic MIM#219800\nReview for gene: CTNS was set to GREEN\ngene: CTNS was marked as current diagnostic\nAdded comment: Hypophosphatemic rickets is a prominent feature of cystinosis when untreated. \nSources: Expert list","entity_name":"CTNS","entity_type":"gene"},{"created":"2021-10-08T14:21:09.058056+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.26","user_name":"Bryony Thompson","item_type":"entity","text":"Marked gene: SGK3 as ready","entity_name":"SGK3","entity_type":"gene"},{"created":"2021-10-08T14:21:09.046831+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.26","user_name":"Bryony Thompson","item_type":"entity","text":"Gene: sgk3 has been classified as Red List (Low Evidence).","entity_name":"SGK3","entity_type":"gene"},{"created":"2021-10-08T14:19:26.551681+11:00","panel_name":"Hypophosphataemic Rickets","panel_id":122,"panel_version":"0.26","user_name":"Bryony Thompson","item_type":"entity","text":"reviewed gene: SGK3: Rating: RED; Mode of pathogenicity: None; Publications: 31821448; Phenotypes: Hypophosphatemic rickets; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"SGK3","entity_type":"gene"},{"created":"2021-10-08T13:57:00.239201+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1275","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TSPYL1 as ready","entity_name":"TSPYL1","entity_type":"gene"},{"created":"2021-10-08T13:57:00.228315+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1275","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tspyl1 has been classified as Green List (High Evidence).","entity_name":"TSPYL1","entity_type":"gene"},{"created":"2021-10-08T13:56:56.102659+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1275","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TSPYL1 as Green List (high evidence)","entity_name":"TSPYL1","entity_type":"gene"},{"created":"2021-10-08T13:56:56.094019+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1275","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tspyl1 has been classified as Green List (High Evidence).","entity_name":"TSPYL1","entity_type":"gene"},{"created":"2021-10-08T13:55:33.961330+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.95","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: USP48 as ready","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:55:33.950168+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.95","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp48 has been classified as Green List (High Evidence).","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:54:52.765471+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.95","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: USP48 as Green List (high evidence)","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:54:52.756344+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.95","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp48 has been classified as Green List (High Evidence).","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:54:22.784880+11:00","panel_name":"Deafness_IsolatedAndComplex","panel_id":209,"panel_version":"1.94","user_name":"Zornitza Stark","item_type":"entity","text":"gene: USP48 was added\ngene: USP48 was added to Deafness_IsolatedAndComplex. Sources: Literature\nMode of inheritance for gene: USP48 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: USP48 were set to 34059922\nPhenotypes for gene: USP48 were set to Nonsyndromic genetic deafness, MONDO:0019497\nReview for gene: USP48 was set to GREEN\nAdded comment: PMID: 34059922 - Bassani et al 2021 - 3 cases reported with variants in USP48 and non syndromic hearing loss. They first analysed 4-generation Italian family with 6 individuals with hearing loss. The only rare variant segregating with the disease was a missense variant in USP48 (NM_032234.7:c.1216G > A, NP_115612.4:p.(Gly406Arg)). The variant is present in GnomAD v2.1.1 with a minor allele frequency (MAF) of 6.7 × 10−5 (17 allele out of 251 304 with no homozygotes). They also observed one hearing individual in the family who was heterozygous for the variant, suggesting incomplete penetrance.\r\nIn a Dutch family the found by exome sequencing a missense variant in USP48 (NM_032236.7:c.2215_2216delinsTT, NP_115612.4:p.(Thr739Leu)). The probands mother and uncle were also affected by no sequence data was available for analysis.\r\nIn a French family a proband is reported with right profound sensorineural hearing impairment (at 12 months), but normal left hearing (at 6 years old). The patient is heterozygote for a de novo splice variant in USP48 (NM_032236.7:c.3058 + 2 T > C, NP_115612.4:p.?;) which is not found in GnomAD and is predicted to result in a frameshift resulting in either NMD or a truncated protein.\r\nIn functional experiments they showed that the two missense variants found in the Italian and Dutch families, and a shortened protein as predicted for the variant found in the French variant, showed an impaired ability to cleave tetra-ubiquitin into tri-, di- and mono-ubiquitin. Using immunohistology, they show that the human USP48 protein is present in fetal inner ear specimens.\r\nIn addition zebrafish lacking usp48 showed a significant decrease of auditory response in acoustic startle response assays at 600 and 800 Hz wavelengths. \r\n\r\nOverall, borderline Green: one of the variants is present at a high frequency in the normal population. However, even if just two families are considered, supportive functional data including zebrafish model. \nSources: Literature","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:43:15.960156+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9355","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: USP48 as ready","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:43:15.952666+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9355","user_name":"Zornitza Stark","item_type":"entity","text":"Added comment: Comment when marking as ready: Borderline Green: one of the variants is present at a high frequency in the normal population. However, even if just two families are considered, supportive functional data including zebrafish model.","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:43:15.913431+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9355","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp48 has been classified as Green List (High Evidence).","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:42:09.142449+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9355","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: USP48 as Green List (high evidence)","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:42:09.133409+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9355","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: usp48 has been classified as Green List (High Evidence).","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-08T13:38:33.938942+11:00","panel_name":"Pulmonary Fibrosis_Interstitial Lung Disease","panel_id":162,"panel_version":"0.33","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MARS as ready","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:38:33.933145+11:00","panel_name":"Pulmonary Fibrosis_Interstitial Lung Disease","panel_id":162,"panel_version":"0.33","user_name":"Zornitza Stark","item_type":"entity","text":"Added comment: Comment when marking as ready: New HGNC approved name is MARS1.","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:38:33.902875+11:00","panel_name":"Pulmonary Fibrosis_Interstitial Lung Disease","panel_id":162,"panel_version":"0.33","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mars has been classified as Green List (High Evidence).","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:38:16.840908+11:00","panel_name":"Pulmonary Fibrosis_Interstitial Lung Disease","panel_id":162,"panel_version":"0.33","user_name":"Zornitza Stark","item_type":"entity","text":"Tag new gene name tag was added to gene: MARS.","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:37:56.431312+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9354","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MARS as ready","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:37:56.426368+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9354","user_name":"Zornitza Stark","item_type":"entity","text":"Added comment: Comment when marking as ready: New HGNC approved gene name is MARS1.","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:37:56.394742+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9354","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mars has been classified as Green List (High Evidence).","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:37:30.981505+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9354","user_name":"Zornitza Stark","item_type":"entity","text":"Tag new gene name tag was added to gene: MARS.","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:37:13.159715+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MARS as ready","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:37:13.155440+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"Added comment: Comment when marking as ready: New HGNC approved name is MARS1.","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:37:13.132438+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mars has been classified as Red List (Low Evidence).","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:36:34.442267+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"Tag new gene name tag was added to gene: MARS.","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:36:00.562135+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MARS as ready","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:36:00.549542+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mars has been classified as Red List (Low Evidence).","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:35:51.895321+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MARS was added\ngene: MARS was added to Chromosome Breakage Disorders. Sources: Literature\nMode of inheritance for gene: MARS was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: MARS were set to 33909043\nPhenotypes for gene: MARS were set to Trichothiodystrophy, MONDO:0018053\nReview for gene: MARS was set to RED\nAdded comment: Bi-allelic ariants in this gene are associated with interstitial and liver disease.\r\n\r\nPMID: 33909043 - Botta et al 2021 - using WES/WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified a homozygous variant in one Italian patient (c.1201G > A (p.Val401Me) that is very rare (gnomAD frequency 0.00001414). Functional studies suggest that the variant affects gene product stability.\r\n\r\nAlthough chromosome breakage is unlikely to be the underlying mechanism, included in this panel for completeness with a Red rating (one individual reported). \nSources: Literature","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:32:11.123021+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9354","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MARS as ready","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:32:11.111743+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9354","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mars has been classified as Green List (High Evidence).","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:31:48.047833+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9354","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MARS were changed from  to Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy, MONDO:0018053","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:31:11.106481+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9353","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MARS were set to ","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:30:47.159737+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9352","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: MARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:29:24.702146+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9351","user_name":"Zornitza Stark","item_type":"entity","text":"changed review comment from: Association with CMT: Two families reported. One mutation positive family member was asymptomatic. Second case is proband only testing with no segregation or functional data. Note one of the variants identified in dominant MARS1-associated neuropathy, p.Arg618Cys, has also been reported in AR MARS1-related pulmonary interstiatial/liver disease.; to: Association with CMT and mono-allelic variants: Two families reported. One mutation positive family member was asymptomatic. Second case is proband only testing with no segregation or functional data. Note one of the variants identified in dominant MARS1-associated neuropathy, p.Arg618Cys, has also been reported in AR MARS1-related pulmonary interstiatial/liver disease.","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:29:13.000269+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9351","user_name":"Zornitza Stark","item_type":"entity","text":"changed review comment from: Association with interstitial lung and liver disease: More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.\r\n\r\nPathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis.; to: Association with interstitial lung and liver disease and bi-allelic variants: More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.\r\n\r\nPathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis.","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:28:40.772504+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9351","user_name":"Zornitza Stark","item_type":"entity","text":"changed review comment from: Two families reported. One mutation positive family member was asymptomatic. Second case is proband only testing with no segregation or functional data. Note one of the variants identified in dominant MARS1-associated neuropathy, p.Arg618Cys, has also been reported in AR MARS1-related pulmonary interstiatial/liver disease.; to: Association with CMT: Two families reported. One mutation positive family member was asymptomatic. Second case is proband only testing with no segregation or functional data. Note one of the variants identified in dominant MARS1-associated neuropathy, p.Arg618Cys, has also been reported in AR MARS1-related pulmonary interstiatial/liver disease.","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T13:28:17.014948+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9351","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MARS: Added comment: Association with interstitial lung and liver disease: More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.\r\n\r\nPathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis.; Changed rating: GREEN; Changed publications: 23729695, 24354524, 29655802, 24103465, 25913036; Changed phenotypes: Interstitial lung and liver disease, MIM#615486, Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-08T10:50:42.909073+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1274","user_name":"Krithika Murali","item_type":"entity","text":"gene: TSPYL1 was added\ngene: TSPYL1 was added to Genetic Epilepsy. Sources: Expert list,Literature\nMode of inheritance for gene: TSPYL1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TSPYL1 were set to 32885560; 15273283; 33075815\nPhenotypes for gene: TSPYL1 were set to Sudden infant death with dysgenesis of the testes syndrome - 608800; sudden infant death-dysgenesis of the testes syndrome MONDO:0012124\nReview for gene: TSPYL1 was set to GREEN\nAdded comment: First identified in a large Amish family - lethal disease characterized by sudden infant death from cardiorespiratory arrest with dysgenesis of the testes (Puffenberger et al 2004).  Cases in non-Amish families reported with additional phenotypic features noted including epilepsy (Slater et al 2020 and Buyse et al 2020) \nSources: Expert list, Literature","entity_name":"TSPYL1","entity_type":"gene"},{"created":"2021-10-08T10:48:58.756489+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.7","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: AARS as ready","entity_name":"AARS","entity_type":"gene"},{"created":"2021-10-08T10:48:58.746080+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.7","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: aars has been classified as Amber List (Moderate Evidence).","entity_name":"AARS","entity_type":"gene"},{"created":"2021-10-08T10:48:54.412663+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.7","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: AARS as Amber List (moderate evidence)","entity_name":"AARS","entity_type":"gene"},{"created":"2021-10-08T10:48:54.402435+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.7","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: aars has been classified as Amber List (Moderate Evidence).","entity_name":"AARS","entity_type":"gene"},{"created":"2021-10-08T10:48:29.964148+11:00","panel_name":"Chromosome Breakage Disorders","panel_id":79,"panel_version":"1.6","user_name":"Zornitza Stark","item_type":"entity","text":"gene: AARS was added\ngene: AARS was added to Chromosome Breakage Disorders. Sources: Literature\nMode of inheritance for gene: AARS was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: AARS were set to 33909043\nPhenotypes for gene: AARS were set to Trichothiodystrophy, MONDO:0018053\nReview for gene: AARS was set to AMBER\nAdded comment: PMID: 33909043 - Botta et al 2021 - using WES or WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified 2 unrelated cases carrying 4 potentially pathogenic variants in the AARS1 gene (previously known as AARSB). Both patients had very rare compound heterozygous missense variants. In one family there was an older affected sibling but segregation data was not available for either family. Functional studies suggest that the variants affects gene product stability.\r\n\r\nAmber rating as 2 families only, and uncertain of underlying mechanism (unlikely chromosome breakage, gene is associated with other disease entities) but included due to phenotypic overlap. \nSources: Literature","entity_name":"AARS","entity_type":"gene"},{"created":"2021-10-08T10:45:03.699397+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9351","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: AARS were changed from Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287 to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053","entity_name":"AARS","entity_type":"gene"},{"created":"2021-10-08T10:44:43.761052+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9350","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: AARS were set to 28493438; 25817015; 20045102; 22009580; 22206013; 30373780; 26032230","entity_name":"AARS","entity_type":"gene"},{"created":"2021-10-08T10:26:42.130913+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4194","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: CELF2 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 97, MIM#619561","entity_name":"CELF2","entity_type":"gene"},{"created":"2021-10-08T10:26:18.073947+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1274","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: CELF2 were changed from Developmental and epileptic encephalopathy 97, MIM#619561 to Developmental and epileptic encephalopathy 97, MIM#619561","entity_name":"CELF2","entity_type":"gene"},{"created":"2021-10-08T10:26:04.979769+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4193","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: CELF2: Changed phenotypes: Developmental and epileptic encephalopathy 97, MIM#619561","entity_name":"CELF2","entity_type":"gene"},{"created":"2021-10-08T10:25:48.263663+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1274","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: CELF2 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 97, MIM#619561","entity_name":"CELF2","entity_type":"gene"},{"created":"2021-10-08T10:24:53.934433+11:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1273","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: CELF2: Changed phenotypes: Developmental and epileptic encephalopathy 97, MIM#619561","entity_name":"CELF2","entity_type":"gene"},{"created":"2021-10-08T10:24:35.170336+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9349","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: CELF2 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 97, MIM#619561","entity_name":"CELF2","entity_type":"gene"},{"created":"2021-10-08T10:24:03.017494+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9348","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: CELF2: Changed phenotypes: Developmental and epileptic encephalopathy 97, MIM#619561","entity_name":"CELF2","entity_type":"gene"},{"created":"2021-10-08T10:13:41.062985+11:00","panel_name":"Defects of innate immunity","panel_id":231,"panel_version":"0.81","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SPPL2A were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency 86, MIM#619549; Susceptibility to mycobacteria and Salmonella","entity_name":"SPPL2A","entity_type":"gene"},{"created":"2021-10-08T10:13:06.912338+11:00","panel_name":"Defects of innate immunity","panel_id":231,"panel_version":"0.80","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: SPPL2A: Changed phenotypes: Immunodeficiency 86, MIM#619549, Susceptibility to mycobacteria and Salmonella","entity_name":"SPPL2A","entity_type":"gene"},{"created":"2021-10-08T10:12:49.228409+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9348","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SPPL2A were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency 86, MIM#619549; Susceptibility to mycobacteria and Salmonella","entity_name":"SPPL2A","entity_type":"gene"},{"created":"2021-10-08T10:12:25.007899+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9347","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: SPPL2A: Changed phenotypes: Immunodeficiency 86, MIM#619549, Susceptibility to mycobacteria and Salmonella","entity_name":"SPPL2A","entity_type":"gene"},{"created":"2021-10-08T00:30:30.423758+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9347","user_name":"Eleanor Williams","item_type":"entity","text":"gene: USP48 was added\ngene: USP48 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: USP48 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: USP48 were set to 34059922\nPhenotypes for gene: USP48 were set to non-syndromic hearing loss; nonsyndromic genetic deafness, MONDO:0019497\nPenetrance for gene: USP48 were set to Incomplete\nReview for gene: USP48 was set to GREEN\nAdded comment: PMID: 34059922 - Bassani et al 2021 - 3 cases reported with variants in USP48 and non syndromic hearing loss. They first analysed 4-generation Italian family with 6 individuals with hearing loss. The only rare variant segregating with the disease was a missense variant in USP48 (NM_032234.7:c.1216G > A, NP_115612.4:p.(Gly406Arg)). The variant is present in GnomAD v2.1.1 with a minor allele frequency (MAF) of 6.7 × 10−5 (17 allele out of 251 304 with no homozygotes). They also observed one hearing individual in the family who was heterozygous for the variant, suggesting incomplete penetrance.\r\nIn a Dutch family the found by exome sequencing a missense variant in USP48 (NM_032236.7:c.2215_2216delinsTT, NP_115612.4:p.(Thr739Leu)). The probands mother and uncle were also affected by no sequence data was available for analysis.\r\nIn a French family a proband is reported with right profound sensorineural hearing impairment (at 12 months), but normal left hearing (at 6 years old). The patient is heterozygote for a de novo splice variant in USP48 (NM_032236.7:c.3058 + 2 T > C, NP_115612.4:p.?;) which is not found in GnomAD and is predicted to result in a frameshift resulting in either NMD or a truncated protein.\r\nIn functional experiments they showed that the two missense variants found in the Italian and Dutch families, and a shortened protein as predicted for the variant found in the French variant, showed an impaired ability to cleave tetra-ubiquitin into tri-, di- and mono-ubiquitin. Using immunohistology, they show that the human USP48 protein is present in fetal inner ear specimens.\r\nIn addition zebrafish lacking usp48 showed a significant decrease of auditory response in acoustic startle response assays at 600 and 800 Hz wavelengths. \nSources: Literature","entity_name":"USP48","entity_type":"gene"},{"created":"2021-10-07T23:11:45.986272+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9347","user_name":"Eleanor Williams","item_type":"entity","text":"reviewed gene: MARS: Rating: ; Mode of pathogenicity: None; Publications: 33909043; Phenotypes: trichothiodystrophy, MONDO:0018053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"MARS","entity_type":"gene"},{"created":"2021-10-07T23:09:19.130621+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.9347","user_name":"Eleanor Williams","item_type":"entity","text":"changed review comment from: PMID: 33909043 - Botta et al 2021 - using WES or WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified 2 unrelated cases carrying 4 potentially pathogenic variants in the AARS1 gene (previously known as AARSB. Both patients had very rare compound heterozygous missense variants. In one family there was an older affected sibling but segregation data was not available for either family.; to: PMID: 33909043 - Botta et al 2021 - using WES or WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified 2 unrelated cases carrying 4 potentially pathogenic variants in the AARS1 gene (previously known as AARSB. Both patients had very rare compound heterozygous missense variants. In one family there was an older affected sibling but segregation data was not available for either family. Functional studies suggest that the variants affects gene product stability.","entity_name":"AARS","entity_type":"gene"}]}