{"count":221415,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=354","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=352","results":[{"created":"2024-11-07T17:06:40.119397+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6647","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PEX10 were changed from  to Peroxisome biogenesis disorder 6A (Zellweger) MIM#614870; Peroxisome biogenesis disorder 6B MIM#614871","entity_name":"PEX10","entity_type":"gene"},{"created":"2024-11-07T17:06:07.376458+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6646","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PEX10 were set to ","entity_name":"PEX10","entity_type":"gene"},{"created":"2024-11-07T17:05:40.666898+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6646","user_name":"Ain Roesley","item_type":"entity","text":"Mode of inheritance for gene: PEX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"PEX10","entity_type":"gene"},{"created":"2024-11-07T17:04:56.593562+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6645","user_name":"Ain Roesley","item_type":"entity","text":"reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger) MIM#614870, Peroxisome biogenesis disorder 6B MIM#614871; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"PEX10","entity_type":"gene"},{"created":"2024-11-07T17:03:34.991516+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6645","user_name":"Ain Roesley","item_type":"entity","text":"Marked gene: PEX1 as ready","entity_name":"PEX1","entity_type":"gene"},{"created":"2024-11-07T17:03:34.979481+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6645","user_name":"Ain Roesley","item_type":"entity","text":"Gene: pex1 has been classified as Green List (High Evidence).","entity_name":"PEX1","entity_type":"gene"},{"created":"2024-11-07T17:03:02.710608+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6645","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PEX1 were set to ","entity_name":"PEX1","entity_type":"gene"},{"created":"2024-11-07T17:02:37.816558+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6645","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PEX1 were changed from  to Heimler syndrome 1 MIM#234580; Peroxisome biogenesis disorder 1A (Zellweger) MIM#214100; Peroxisome biogenesis disorder 1B (NALD/IRD) MIM#601539","entity_name":"PEX1","entity_type":"gene"},{"created":"2024-11-07T17:02:14.708038+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6645","user_name":"Ain Roesley","item_type":"entity","text":"Mode of inheritance for gene: PEX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"PEX1","entity_type":"gene"},{"created":"2024-11-07T17:01:33.052954+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6644","user_name":"Ain Roesley","item_type":"entity","text":"edited their review of gene: PEX1: Changed rating: GREEN","entity_name":"PEX1","entity_type":"gene"},{"created":"2024-11-07T17:01:21.867399+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6644","user_name":"Ain Roesley","item_type":"entity","text":"reviewed gene: PEX1: Rating: ; Mode of pathogenicity: None; Publications: 20301621; Phenotypes: Heimler syndrome 1 MIM#234580, Peroxisome biogenesis disorder 1A (Zellweger) MIM#214100, Peroxisome biogenesis disorder 1B (NALD/IRD) MIM#601539; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"PEX1","entity_type":"gene"},{"created":"2024-11-07T16:59:54.732546+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6644","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PEPD were set to 26110198; 32455636","entity_name":"PEPD","entity_type":"gene"},{"created":"2024-11-07T16:59:32.663397+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6644","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PEPD were changed from Prolidase deficiency MIM#170100 to Prolidase deficiency MIM#170100","entity_name":"PEPD","entity_type":"gene"},{"created":"2024-11-07T16:59:23.054573+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6643","user_name":"Ain Roesley","item_type":"entity","text":"Marked gene: PEPD as ready","entity_name":"PEPD","entity_type":"gene"},{"created":"2024-11-07T16:59:23.033342+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6643","user_name":"Ain Roesley","item_type":"entity","text":"Gene: pepd has been classified as Green List (High Evidence).","entity_name":"PEPD","entity_type":"gene"},{"created":"2024-11-07T16:59:03.575923+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6643","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PEPD were changed from  to Prolidase deficiency MIM#170100","entity_name":"PEPD","entity_type":"gene"},{"created":"2024-11-07T16:58:38.197280+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6643","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PEPD were set to ","entity_name":"PEPD","entity_type":"gene"},{"created":"2024-11-07T16:58:09.068935+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6643","user_name":"Ain Roesley","item_type":"entity","text":"Mode of inheritance for gene: PEPD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"PEPD","entity_type":"gene"},{"created":"2024-11-07T16:57:24.446076+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6642","user_name":"Ain Roesley","item_type":"entity","text":"reviewed gene: PEPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 26110198, 32455636; Phenotypes: Prolidase deficiency MIM#170100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"PEPD","entity_type":"gene"},{"created":"2024-11-07T16:55:52.210356+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6642","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDSS2 were changed from Coenzyme Q10 deficiency, primary, 3 MIM#614652 to Coenzyme Q10 deficiency, primary, 3 MIM#614652","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:55:31.423351+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6641","user_name":"Ain Roesley","item_type":"entity","text":"Marked gene: PDSS2 as ready","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:55:31.409499+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6641","user_name":"Ain Roesley","item_type":"entity","text":"Gene: pdss2 has been classified as Red List (Low Evidence).","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:55:20.683867+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6641","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDSS2 were changed from Coenzyme Q10 deficiency, primary, 3 MIM#614652 to Coenzyme Q10 deficiency, primary, 3 MIM#614652","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:54:52.738252+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6640","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDSS2 were changed from  to Coenzyme Q10 deficiency, primary, 3 MIM#614652","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:54:28.315390+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6640","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PDSS2 were set to ","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:54:03.110583+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6639","user_name":"Ain Roesley","item_type":"entity","text":"Mode of inheritance for gene: PDSS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:53:38.463874+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6639","user_name":"Ain Roesley","item_type":"entity","text":"Classified gene: PDSS2 as Red List (low evidence)","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:53:38.449185+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6639","user_name":"Ain Roesley","item_type":"entity","text":"Gene: pdss2 has been classified as Red List (Low Evidence).","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:52:58.561319+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6638","user_name":"Ain Roesley","item_type":"entity","text":"reviewed gene: PDSS2: Rating: RED; Mode of pathogenicity: None; Publications: 28125198, 29032433, 25349199, 17186472, 21723727, 10972372; Phenotypes: Coenzyme Q10 deficiency, primary, 3 MIM#614652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"PDSS2","entity_type":"gene"},{"created":"2024-11-07T16:46:41.081986+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6638","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDHX were changed from Lacticacidemia due to PDX1 deficiency MIM#245349 to Lacticacidemia due to PDX1 deficiency MIM#245349","entity_name":"PDHX","entity_type":"gene"},{"created":"2024-11-07T16:46:34.937551+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6638","user_name":"Ain Roesley","item_type":"entity","text":"Marked gene: PDHX as ready","entity_name":"PDHX","entity_type":"gene"},{"created":"2024-11-07T16:46:34.926498+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6638","user_name":"Ain Roesley","item_type":"entity","text":"Gene: pdhx has been classified as Green List (High Evidence).","entity_name":"PDHX","entity_type":"gene"},{"created":"2024-11-07T16:46:15.242291+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6638","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDHX were changed from Lacticacidemia due to PDX1 deficiency MIM#245349 to Lacticacidemia due to PDX1 deficiency MIM#245349","entity_name":"PDHX","entity_type":"gene"},{"created":"2024-11-07T16:45:51.628828+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6638","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDHX were changed from  to Lacticacidemia due to PDX1 deficiency MIM#245349","entity_name":"PDHX","entity_type":"gene"},{"created":"2024-11-07T16:45:23.928767+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6637","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PDHX were set to ","entity_name":"PDHX","entity_type":"gene"},{"created":"2024-11-07T16:44:53.834259+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6637","user_name":"Ain Roesley","item_type":"entity","text":"Mode of inheritance for gene: PDHX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"PDHX","entity_type":"gene"},{"created":"2024-11-07T16:44:12.273735+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6636","user_name":"Ain Roesley","item_type":"entity","text":"reviewed gene: PDHX: Rating: GREEN; Mode of pathogenicity: None; Publications: 34138529; Phenotypes: Lacticacidemia due to PDX1 deficiency MIM#245349; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"PDHX","entity_type":"gene"},{"created":"2024-11-07T16:41:36.613724+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.546","user_name":"Lauren Thomas","item_type":"entity","text":"reviewed gene: ALS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24315819, 12601111, 30128655, 33409823; Phenotypes: Infantile onset ascending spastic paralysis (MIM#607225), Juvenile amyotrophic lateral sclerosis 2 (MIM#205100), Juvenile primary lateral sclerosis (MIM#606353); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ALS2","entity_type":"gene"},{"created":"2024-11-07T16:38:47.086239+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6636","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PDHA1 were set to 23021068","entity_name":"PDHA1","entity_type":"gene"},{"created":"2024-11-07T16:38:44.118784+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6636","user_name":"Ain Roesley","item_type":"entity","text":"Marked gene: PDHA1 as ready","entity_name":"PDHA1","entity_type":"gene"},{"created":"2024-11-07T16:38:44.103540+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6636","user_name":"Ain Roesley","item_type":"entity","text":"Gene: pdha1 has been classified as Green List (High Evidence).","entity_name":"PDHA1","entity_type":"gene"},{"created":"2024-11-07T16:38:18.793759+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6636","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDHA1 were changed from Pyruvate dehydrogenase E1-alpha deficiency MIM#312170 to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170","entity_name":"PDHA1","entity_type":"gene"},{"created":"2024-11-07T16:37:50.899687+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6635","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDHA1 were changed from  to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170","entity_name":"PDHA1","entity_type":"gene"},{"created":"2024-11-07T16:37:21.884160+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6635","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PDHA1 were set to ","entity_name":"PDHA1","entity_type":"gene"},{"created":"2024-11-07T16:36:53.975930+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6635","user_name":"Ain Roesley","item_type":"entity","text":"Mode of inheritance for gene: PDHA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)","entity_name":"PDHA1","entity_type":"gene"},{"created":"2024-11-07T16:36:14.105296+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6634","user_name":"Ain Roesley","item_type":"entity","text":"changed review comment from: In subjects surviving past 6 months, a broad range of intellectual outcomes was observed.; to: ID is a feature of this condition.\r\n\r\nPMID:23021068 \"In subjects surviving past 6 months, a broad range of intellectual outcomes was observed.\"","entity_name":"PDHA1","entity_type":"gene"},{"created":"2024-11-07T16:35:48.393907+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6634","user_name":"Ain Roesley","item_type":"entity","text":"reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23021068; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency MIM#312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes","entity_name":"PDHA1","entity_type":"gene"},{"created":"2024-11-07T16:26:51.011586+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2090","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: SLC24A1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008419; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SLC24A1","entity_type":"gene"},{"created":"2024-11-07T16:19:42.155977+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2090","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: C1QTNF5: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008422; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"C1QTNF5","entity_type":"gene"},{"created":"2024-11-07T16:16:52.815753+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6634","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MED16 as ready","entity_name":"MED16","entity_type":"gene"},{"created":"2024-11-07T16:16:52.805420+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6634","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: med16 has been classified as Green List (High Evidence).","entity_name":"MED16","entity_type":"gene"},{"created":"2024-11-07T16:14:58.490701+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2090","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: EPHB2: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008367; Phenotypes: bleeding disorder, platelet-type, 22 MONDO:0032765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"EPHB2","entity_type":"gene"},{"created":"2024-11-07T16:07:19.873388+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.546","user_name":"Lauren Thomas","item_type":"entity","text":"reviewed gene: ALG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26931382, 24157261, 14973782; Phenotypes: Congenital disorder of glycosylation, type Ik, MIM# 608540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ALG1","entity_type":"gene"},{"created":"2024-11-07T15:59:25.956066+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2090","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: F12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hereditary angioedema type 3 MONDO:0012526; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"F12","entity_type":"gene"},{"created":"2024-11-07T15:57:18.635680+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2090","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: HOXA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 11101832; Phenotypes: radioulnar synostosis with amegakaryocytic thrombocytopenia 1 MONDO:0024558; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"HOXA11","entity_type":"gene"},{"created":"2024-11-07T15:50:40.453861+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2090","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: CCDC115: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008374; Phenotypes: CCDC115-CDG MONDO:0014789; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"CCDC115","entity_type":"gene"},{"created":"2024-11-07T15:50:16.018932+11:00","panel_name":"Defects of innate immunity","panel_id":231,"panel_version":"0.138","user_name":"Chirag Patel","item_type":"entity","text":"Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, no OMIM #","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T15:49:49.971867+11:00","panel_name":"Defects of innate immunity","panel_id":231,"panel_version":"0.138","user_name":"Chirag Patel","item_type":"entity","text":"Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, no OMIM #","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T15:49:12.905561+11:00","panel_name":"Defects of innate immunity","panel_id":231,"panel_version":"0.137","user_name":"Chirag Patel","item_type":"entity","text":"Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, no OMIM #","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T15:48:56.259209+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2090","user_name":"Chirag Patel","item_type":"entity","text":"Phenotypes for gene: IRAK2 were changed from Immune dysregulation, no OMIM # to Immune dysregulation, no OMIM #","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T15:48:47.240408+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2090","user_name":"Chirag Patel","item_type":"entity","text":"Phenotypes for gene: IRAK2 were changed from Immunodeficiency, no OMIM # to Immune dysregulation, no OMIM #","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T15:48:16.382316+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2089","user_name":"Chirag Patel","item_type":"entity","text":"changed review comment from: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria. \r\n\r\nIndividual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported.\r\n\r\nIndividual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.\r\n\r\nBoth patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens).\r\n\r\nPaper does not comment on reasons for disease in biallelic and mono-allelic form. \nSources: Literature; to: PMID: 39299377\r\n2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria.\r\n\r\nIndividual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported. Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.\r\n\r\nBoth patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens). Paper does not comment on reasons for disease in biallelic and mono-allelic form.\r\n\r\n\r\nPreprint paper:\r\n2 individuals with immune dysregulation (1 x systemic lupus erythematosus and 1 x autoinflammatory disease) with same homozgyous exon 2 deletion in IRAK2 gene found on WES testing and confirmed with Sanger sequencing. Unaffected family members in trio were heterozygous for variant. Exon 2 encodes a proportion of the death domain, a critical protein domain for Myddosome assembly.\r\n\r\nThe patients exhibited aberrantly upregulated type I interferon (IFN) response following LPS stimulation, which was further confirmed in bone marrow-derived macrophages (BMDMs) in mice. RNA sequencing analysis indicated that PBMCs from the two patients consistently exhibited defects in activating NFkb signaling in response to LPS or R848 stimulation, as well as impaired activation of the MAPK signaling pathway. RNA sequencing demonstrated that BMDMs from Irak2 ∆ex2/∆ex2 mice exhibited defects in NFkb and MAPK signaling pathways, similar to patients’ PBMCs.","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T15:48:10.154810+11:00","panel_name":"Systemic Autoinflammatory Disease_Periodic Fever","panel_id":238,"panel_version":"1.53","user_name":"Chirag Patel","item_type":"entity","text":"gene: IRAK2 was added\ngene: IRAK2 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature\nMode of inheritance for gene: IRAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: IRAK2 were set to PMID: 39299377\nPhenotypes for gene: IRAK2 were set to Immune dysregulation, no OMIM #\nReview for gene: IRAK2 was set to RED\nAdded comment: PMID: 39299377\r\n2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria.\r\n\r\nIndividual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported. Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.\r\n\r\nBoth patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens). Paper does not comment on reasons for disease in biallelic and mono-allelic form.\r\n\r\n\r\nPreprint paper:\r\n2 individuals with immune dysregulation (1 x systemic lupus erythematosus and 1 x autoinflammatory disease) with same homozgyous exon 2 deletion in IRAK2 gene found on WES testing and confirmed with Sanger sequencing. Unaffected family members in trio were heterozygous for variant. Exon 2 encodes a proportion of the death domain, a critical protein domain for Myddosome assembly.\r\n\r\nThe patients exhibited aberrantly upregulated type I interferon (IFN) response following LPS stimulation, which was further confirmed in bone marrow-derived macrophages (BMDMs) in mice. RNA sequencing analysis indicated that PBMCs from the two patients consistently exhibited defects in activating NFkb signaling in response to LPS or R848 stimulation, as well as impaired activation of the MAPK signaling pathway. RNA sequencing demonstrated that BMDMs from Irak2 ∆ex2/∆ex2 mice exhibited defects in NFkb and MAPK signaling pathways, similar to patients’ PBMCs. \nSources: Literature","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T15:47:05.824646+11:00","panel_name":"Defects of innate immunity","panel_id":231,"panel_version":"0.136","user_name":"Chirag Patel","item_type":"entity","text":"Phenotypes for gene: IRAK2 were changed from  to Immune dysregulation, no OMIM #","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T15:46:00.689814+11:00","panel_name":"Defects of innate immunity","panel_id":231,"panel_version":"0.135","user_name":"Chirag Patel","item_type":"entity","text":"changed review comment from: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria. \r\n\r\nIndividual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported.\r\n\r\nIndividual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.\r\n\r\nBoth patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens).\r\n\r\nPaper does not comment on reasons for disease in biallelic and mono-allelic form. \nSources: Literature; to: PMID: 39299377\r\n2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria. \r\n\r\nIndividual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported. Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.\r\n\r\nBoth patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens). Paper does not comment on reasons for disease in biallelic and mono-allelic form. \r\n\r\n\r\nPreprint paper:\r\n2 individuals with immune dysregulation (1 x systemic lupus erythematosus and 1 x autoinflammatory disease) with same homozgyous exon 2 deletion in IRAK2 gene found on WES testing and confirmed with Sanger sequencing. Unaffected family members in trio were heterozygous for variant. Exon 2 encodes a proportion of the death domain, a critical protein domain for Myddosome assembly.\r\n\r\nThe patients exhibited aberrantly upregulated type I interferon (IFN) response following LPS stimulation, which was further confirmed in bone marrow-derived macrophages (BMDMs) in mice. RNA sequencing analysis indicated that PBMCs from the two patients consistently exhibited defects in activating NFkb signaling in response to LPS or R848 stimulation, as well as impaired activation of the MAPK signaling pathway. RNA sequencing demonstrated that BMDMs from Irak2 ∆ex2/∆ex2 mice exhibited defects in NFkb and MAPK signaling pathways, similar to patients’ PBMCs. \r\n","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T15:42:39.463655+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2089","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: WISP3: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008442; Phenotypes: progressive pseudorheumatoid arthropathy of childhood MONDO:0008827; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"WISP3","entity_type":"gene"},{"created":"2024-11-07T15:36:06.535411+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2089","user_name":"Sangavi Sivagnanasundram","item_type":"entity","text":"reviewed gene: WDR60: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008443; Phenotypes: short-rib thoracic dysplasia 8 with or without polydactyly MONDO:0014214; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"WDR60","entity_type":"gene"},{"created":"2024-11-07T15:35:06.626296+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.546","user_name":"Lauren Thomas","item_type":"entity","text":"reviewed gene: ALDH5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9683595, 14635103, 32402538, 32887777; Phenotypes: Succinic semialdehyde dehydrogenase deficiency, MIM# 271980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ALDH5A1","entity_type":"gene"},{"created":"2024-11-07T14:37:00.254369+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.280","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ICK as ready","entity_name":"ICK","entity_type":"gene"},{"created":"2024-11-07T14:37:00.232271+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.280","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ick has been classified as Green List (High Evidence).","entity_name":"ICK","entity_type":"gene"},{"created":"2024-11-07T14:36:54.851963+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.280","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ICK were changed from  to Endocrine-cerebroosteodysplasia, MIM# 612651","entity_name":"ICK","entity_type":"gene"},{"created":"2024-11-07T14:36:14.669200+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.279","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: ICK was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal","entity_name":"ICK","entity_type":"gene"},{"created":"2024-11-07T14:35:37.375023+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.278","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: ICK: Changed phenotypes: Endocrine-cerebroosteodysplasia, MIM# 612651","entity_name":"ICK","entity_type":"gene"},{"created":"2024-11-07T14:35:18.604721+11:00","panel_name":"Polydactyly","panel_id":159,"panel_version":"0.278","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: ICK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ICK","entity_type":"gene"},{"created":"2024-11-07T13:48:57.641979+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2089","user_name":"Chirag Patel","item_type":"entity","text":"gene: IRAK2 was added\ngene: IRAK2 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: IRAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: IRAK2 were set to PMID: 39299377\nPhenotypes for gene: IRAK2 were set to Immunodeficiency, no OMIM #\nReview for gene: IRAK2 was set to RED\nAdded comment: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria. \r\n\r\nIndividual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported.\r\n\r\nIndividual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.\r\n\r\nBoth patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens).\r\n\r\nPaper does not comment on reasons for disease in biallelic and mono-allelic form. \nSources: Literature","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T13:48:12.973880+11:00","panel_name":"Defects of innate immunity","panel_id":231,"panel_version":"0.135","user_name":"Chirag Patel","item_type":"entity","text":"edited their review of gene: IRAK2: Changed phenotypes: Immunodeficiency, no OMIM #","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T13:47:35.631986+11:00","panel_name":"Defects of innate immunity","panel_id":231,"panel_version":"0.135","user_name":"Chirag Patel","item_type":"entity","text":"gene: IRAK2 was added\ngene: IRAK2 was added to Defects of innate immunity. Sources: Literature\nMode of inheritance for gene: IRAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: IRAK2 were set to PMID: 39299377\nReview for gene: IRAK2 was set to RED\nAdded comment: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria. \r\n\r\nIndividual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported.\r\n\r\nIndividual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported.\r\n\r\nBoth patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens).\r\n\r\nPaper does not comment on reasons for disease in biallelic and mono-allelic form. \nSources: Literature","entity_name":"IRAK2","entity_type":"gene"},{"created":"2024-11-07T13:34:18.942713+11:00","panel_name":"Prepair 1000+","panel_id":3861,"panel_version":"1.546","user_name":"Andrew Coventry","item_type":"entity","text":"reviewed gene: INSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 34965699, 11735220, 12023989, 13302174, 10084586; Phenotypes: Donohue syndrome MIM#246200, Rabson-Mendenhall syndrome MIM#262190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"INSR","entity_type":"gene"},{"created":"2024-11-07T13:24:02.891273+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6634","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PDGFRB were set to 31710779; 35221873","entity_name":"PDGFRB","entity_type":"gene"},{"created":"2024-11-07T13:23:34.865345+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6634","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDGFRB were changed from Kosaki overgrowth syndrome MIM#616592 to Kosaki overgrowth syndrome MIM#616592","entity_name":"PDGFRB","entity_type":"gene"},{"created":"2024-11-07T13:23:07.616656+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6633","user_name":"Ain Roesley","item_type":"entity","text":"Publications for gene: PDGFRB were set to ","entity_name":"PDGFRB","entity_type":"gene"},{"created":"2024-11-07T13:22:42.129281+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6633","user_name":"Ain Roesley","item_type":"entity","text":"Phenotypes for gene: PDGFRB were changed from  to Kosaki overgrowth syndrome MIM#616592","entity_name":"PDGFRB","entity_type":"gene"},{"created":"2024-11-07T13:22:13.432503+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6633","user_name":"Ain Roesley","item_type":"entity","text":"Mode of inheritance for gene: PDGFRB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"PDGFRB","entity_type":"gene"},{"created":"2024-11-07T13:21:34.434202+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6632","user_name":"Ain Roesley","item_type":"entity","text":"Marked gene: PDGFRB as ready","entity_name":"PDGFRB","entity_type":"gene"},{"created":"2024-11-07T13:21:34.422770+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6632","user_name":"Ain Roesley","item_type":"entity","text":"Gene: pdgfrb has been classified as Green List (High Evidence).","entity_name":"PDGFRB","entity_type":"gene"},{"created":"2024-11-07T13:21:18.497239+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6632","user_name":"Ain Roesley","item_type":"entity","text":"reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31710779, 35221873; Phenotypes: Kosaki overgrowth syndrome MIM#616592; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes","entity_name":"PDGFRB","entity_type":"gene"},{"created":"2024-11-07T13:13:44.319161+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2088","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: MARK2 as Green List (high evidence)","entity_name":"MARK2","entity_type":"gene"},{"created":"2024-11-07T13:13:44.307281+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2088","user_name":"Chirag Patel","item_type":"entity","text":"Gene: mark2 has been classified as Green List (High Evidence).","entity_name":"MARK2","entity_type":"gene"},{"created":"2024-11-07T13:13:12.559197+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2087","user_name":"Chirag Patel","item_type":"entity","text":"gene: MARK2 was added\ngene: MARK2 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: MARK2 were set to PMID: 39419027, 39436150\nPhenotypes for gene: MARK2 were set to Neurodevelopmental disorder MONDO:0700092\nMode of pathogenicity for gene: MARK2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: MARK2 was set to GREEN\nAdded comment: 31 individuals with autism spectrum disorder (30/31), intellectual disability/developmental delay (100%), motor delay (62%), speech-language problems (100%), seizure/epilepsy (46%), behaviour disorders (ADHD, aggression, anxiety)(74%), and distinctive facial features (narrow face, abnormal or broad forehead, downslanting palpebral fissures, and large or dysplastic ears).\r\n\r\nWES/WGS identified 25 LOF and 6 missense variants in MARK2 gene (Microtubule affinity-regulating kinase 2) which contributes to establishing neuronal polarity and developing dendritic spines. LOF variants were de novo (16/25), inherited (4/25), or unk (5/25). All 6 missense variants were de novo and clustered in the kinase or KA1 domains.\r\n\r\nThe mRNA and protein expression of MARK2 in PBMCs were significantly lower in affected individuals with LOF variants than in the control group. In vitro expression assay of missense variants supported the effect of MARK2 loss. Proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs) showed MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and disorganization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behaviour. Through the use of RNA sequencing (RNA-seq) and lithium treatment, they linked MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identified lithium as a potential drug for treating MARK2-associated ASD. \nSources: Literature","entity_name":"MARK2","entity_type":"gene"},{"created":"2024-11-07T13:12:31.755347+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6632","user_name":"Ain Roesley","item_type":"entity","text":"reviewed gene: PCNT: Rating: AMBER; Mode of pathogenicity: None; Publications: 34978779; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type II MIM#210720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes","entity_name":"PCNT","entity_type":"gene"},{"created":"2024-11-07T13:06:57.026548+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2086","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: DTNA as Green List (high evidence)","entity_name":"DTNA","entity_type":"gene"},{"created":"2024-11-07T13:06:57.010211+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2086","user_name":"Chirag Patel","item_type":"entity","text":"Gene: dtna has been classified as Green List (High Evidence).","entity_name":"DTNA","entity_type":"gene"},{"created":"2024-11-07T13:06:41.747242+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.77","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: DTNA as Green List (high evidence)","entity_name":"DTNA","entity_type":"gene"},{"created":"2024-11-07T13:06:41.738488+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.77","user_name":"Chirag Patel","item_type":"entity","text":"Gene: dtna has been classified as Green List (High Evidence).","entity_name":"DTNA","entity_type":"gene"},{"created":"2024-11-07T13:06:29.175494+11:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2085","user_name":"Chirag Patel","item_type":"entity","text":"reviewed gene: DTNA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36799992; Phenotypes: Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"DTNA","entity_type":"gene"},{"created":"2024-11-07T13:04:36.247175+11:00","panel_name":"Rhabdomyolysis and Metabolic Myopathy","panel_id":3084,"panel_version":"1.15","user_name":"Chirag Patel","item_type":"entity","text":"Classified gene: DTNA as Amber List (moderate evidence)","entity_name":"DTNA","entity_type":"gene"},{"created":"2024-11-07T13:04:36.234907+11:00","panel_name":"Rhabdomyolysis and Metabolic Myopathy","panel_id":3084,"panel_version":"1.15","user_name":"Chirag Patel","item_type":"entity","text":"Gene: dtna has been classified as Amber List (Moderate Evidence).","entity_name":"DTNA","entity_type":"gene"},{"created":"2024-11-07T13:04:17.190618+11:00","panel_name":"Muscular dystrophy and myopathy_Paediatric","panel_id":141,"panel_version":"1.76","user_name":"Chirag Patel","item_type":"entity","text":"gene: DTNA was added\ngene: DTNA was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature\nMode of inheritance for gene: DTNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: DTNA were set to PMID: 36799992\nPhenotypes for gene: DTNA were set to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322\nMode of pathogenicity for gene: DTNA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: DTNA was set to GREEN\nAdded comment: 12 individuals from 4 unrelated families with 2 different monoallelic DTNA variants in exon 18 and affecting the coiled-coil domain of α-dystrobrevin (DTNA). DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype. \r\n\r\nClinical features with onset between 1st and 4th decades included: myalgia, muscle cramps associated with physical activity, exercise intolerance, and increased serum CK (11/12). Most patients have mild symptoms, only 3 had mild proximal muscle weakness of the lower limbs, and 1 had episode of rhabdomyolysis @20yrs. Muscle biopsies in 8 individuals showed mild myopathic and/or dystrophic features. \r\n\r\nThe 2 variants (p.Glu529Lys and p.Gln523_Glu529del) were found by targeted exome sequencing and confirmed by Sanger sequencing. They segregated with the disorder in the families and were absent in gnomAD. Immunofluorescent analysis of patient muscle samples showed decreased DTNA immunoreactivity at the sarcolemma, as well as variably reduced immunoreactivity of several other dystrophin-glycoprotein complex (DGC) proteins, suggesting that the DTNA variants resulted in overall destabilization of the DG complex within skeletal muscle. \nSources: Literature","entity_name":"DTNA","entity_type":"gene"},{"created":"2024-11-07T13:03:57.045330+11:00","panel_name":"Rhabdomyolysis and Metabolic Myopathy","panel_id":3084,"panel_version":"1.14","user_name":"Chirag Patel","item_type":"entity","text":"gene: DTNA was added\ngene: DTNA was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Literature\nMode of inheritance for gene: DTNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: DTNA were set to PMID: 36799992\nPhenotypes for gene: DTNA were set to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322\nMode of pathogenicity for gene: DTNA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: DTNA was set to GREEN\nAdded comment: 12 individuals from 4 unrelated families with 2 different monoallelic DTNA variants in exon 18 and affecting the coiled-coil domain of α-dystrobrevin (DTNA). DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype. \r\n\r\nClinical features with onset between 1st and 4th decades included: myalgia, muscle cramps associated with physical activity, exercise intolerance, and increased serum CK (11/12). Most patients have mild symptoms, only 3 had mild proximal muscle weakness of the lower limbs, and 1 had episode of rhabdomyolysis @20yrs. Muscle biopsies in 8 individuals showed mild myopathic and/or dystrophic features. \r\n\r\nThe 2 variants (p.Glu529Lys and p.Gln523_Glu529del) were found by targeted exome sequencing and confirmed by Sanger sequencing. They segregated with the disorder in the families and were absent in gnomAD. Immunofluorescent analysis of patient muscle samples showed decreased DTNA immunoreactivity at the sarcolemma, as well as variably reduced immunoreactivity of several other dystrophin-glycoprotein complex (DGC) proteins, suggesting that the DTNA variants resulted in overall destabilization of the DG complex within skeletal muscle. \nSources: Literature","entity_name":"DTNA","entity_type":"gene"},{"created":"2024-11-07T12:46:05.946744+11:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.6632","user_name":"Ain Roesley","item_type":"entity","text":"Mode of inheritance for gene: PCCA was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal","entity_name":"PCCA","entity_type":"gene"}]}