HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 221304,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1682",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1680",
"results": [
{
"created": "2020-08-09T12:59:55.931838+10:00",
"panel_name": "Monogenic Diabetes",
"panel_id": 3093,
"panel_version": "0.4",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: HFE2 as ready",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:59:55.927734+10:00",
"panel_name": "Monogenic Diabetes",
"panel_id": 3093,
"panel_version": "0.4",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: HGNC approved name is HJV.",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:59:55.897948+10:00",
"panel_name": "Monogenic Diabetes",
"panel_id": 3093,
"panel_version": "0.4",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hfe2 has been classified as Green List (High Evidence).",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:59:41.619120+10:00",
"panel_name": "Monogenic Diabetes",
"panel_id": 3093,
"panel_version": "0.4",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Tag new gene name tag was added to gene: HFE2.",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:58:57.816976+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.87",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: HFE2 as ready",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:58:57.805694+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.87",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hfe2 has been classified as Red List (Low Evidence).",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:58:55.263373+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.87",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: HFE2 were changed from to Hemochromatosis, type 2A, MIM# 602390",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:58:39.116743+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.86",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: HFE2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:58:13.611023+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.85",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: HFE2 as Red List (low evidence)",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:58:13.600759+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.85",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hfe2 has been classified as Red List (Low Evidence).",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:57:49.535959+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.84",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Tag new gene name tag was added to gene: HFE2.",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:57:42.329275+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.84",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: HFE2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemochromatosis, type 2A, MIM# 602390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HFE2",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:56:44.669802+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.84",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: HFE as ready",
"entity_name": "HFE",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:56:44.658795+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.84",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hfe has been classified as Red List (Low Evidence).",
"entity_name": "HFE",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:56:41.988260+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.84",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: HFE were changed from to Hemochromatosis, MIM# 235200",
"entity_name": "HFE",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:56:17.656704+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.83",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: HFE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HFE",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:55:54.229130+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.82",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: HFE as Red List (low evidence)",
"entity_name": "HFE",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:55:54.219213+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.82",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hfe has been classified as Red List (Low Evidence).",
"entity_name": "HFE",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:55:27.064883+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.81",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: HFE: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemochromatosis, MIM# 235200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HFE",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:52:57.583827+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.81",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: HAMP as ready",
"entity_name": "HAMP",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:52:57.573170+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.81",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hamp has been classified as Red List (Low Evidence).",
"entity_name": "HAMP",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:52:50.565066+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.81",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: HAMP were changed from to Hemochromatosis, type 2B, MIM# 613313",
"entity_name": "HAMP",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:52:27.500351+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.80",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: HAMP were set to ",
"entity_name": "HAMP",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:52:05.162068+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.79",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: HAMP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HAMP",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:51:41.027437+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.78",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: HAMP as Red List (low evidence)",
"entity_name": "HAMP",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:51:41.015414+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.78",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hamp has been classified as Red List (Low Evidence).",
"entity_name": "HAMP",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:51:19.454636+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.77",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: HAMP: Rating: RED; Mode of pathogenicity: None; Publications: 12469120; Phenotypes: Hemochromatosis, type 2B, MIM# 613313; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HAMP",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:35:31.938203+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.77",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: HADHA as ready",
"entity_name": "HADHA",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:35:31.925816+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.77",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hadha has been classified as Red List (Low Evidence).",
"entity_name": "HADHA",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:35:27.621171+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.77",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: HADHA were changed from to LCHAD deficiency, MIM# 609016; Mitochondrial trifunctional protein deficiency, MIM# 609015",
"entity_name": "HADHA",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:35:06.561882+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.76",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: HADHA were set to ",
"entity_name": "HADHA",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:34:44.719086+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.75",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: HADHA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HADHA",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:34:21.241689+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.74",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: HADHA as Red List (low evidence)",
"entity_name": "HADHA",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:34:21.228446+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.74",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hadha has been classified as Red List (Low Evidence).",
"entity_name": "HADHA",
"entity_type": "gene"
},
{
"created": "2020-08-09T12:33:54.835344+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.73",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: HADHA: Rating: RED; Mode of pathogenicity: None; Publications: 9003853; Phenotypes: LCHAD deficiency, MIM# 609016, Mitochondrial trifunctional protein deficiency, MIM# 609015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HADHA",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:37:50.498714+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3733",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: FAM50A as ready",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:37:50.490511+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3733",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fam50a has been classified as Green List (High Evidence).",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:37:42.250774+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3733",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: FAM50A as Green List (high evidence)",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:37:42.241369+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3733",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fam50a has been classified as Green List (High Evidence).",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:37:25.133188+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3732",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: FAM50A was added\ngene: FAM50A was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: FAM50A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)\nPublications for gene: FAM50A were set to 32703943\nPhenotypes for gene: FAM50A were set to Mental retardation syndrome, X-linked, Armfield type (MIM #300261)\nReview for gene: FAM50A was set to GREEN\nAdded comment: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference. The authors provide clinical details on 6 affected individuals from 5 families. Features included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6). In the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam). In affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40). Missense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3). Previous studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones). Immunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt. Complementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish. Similarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins. Overall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism. Several other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.). \nSources: Literature",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:35:44.604658+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.773",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: FAM50A as ready",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:35:44.584017+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.773",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fam50a has been classified as Amber List (Moderate Evidence).",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:35:40.832655+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.773",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: FAM50A as Amber List (moderate evidence)",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:35:40.824905+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.773",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fam50a has been classified as Amber List (Moderate Evidence).",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:34:48.598918+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.2834",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: FAM50A as ready",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:34:48.589033+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.2834",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fam50a has been classified as Green List (High Evidence).",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:34:43.105520+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.2834",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: FAM50A as Green List (high evidence)",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-09T08:34:43.095538+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.2834",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fam50a has been classified as Green List (High Evidence).",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-08T21:26:51.344176+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.772",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: FAM50A was added\ngene: FAM50A was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: FAM50A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)\nPublications for gene: FAM50A were set to 32703943\nPhenotypes for gene: FAM50A were set to Mental retardation syndrome, X-linked, Armfield type (MIM #300261)\nPenetrance for gene: FAM50A were set to unknown\nReview for gene: FAM50A was set to AMBER\nAdded comment: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference. \r\n\r\nThe authors provide clinical details on 6 affected individuals from 5 families. \r\n\r\nFeatures included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6). \r\n\r\nIn the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam). \r\n\r\nIn affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40).\r\n\r\nMissense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3). \r\n\r\nPrevious studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones). \r\n\r\nImmunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt. \r\n\r\nComplementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish.\r\n\r\nSimilarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins.\r\n\r\nOverall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism. \r\n\r\nSeveral other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.).\r\n\r\nPlease consider inclusion in the ID panel with green rating and epilepsy panel with amber (seizures in individuals from 2 families). \nSources: Literature",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-08T21:26:44.624832+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.2833",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: FAM50A was added\ngene: FAM50A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: FAM50A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)\nPublications for gene: FAM50A were set to 32703943\nPhenotypes for gene: FAM50A were set to Mental retardation syndrome, X-linked, Armfield type (MIM #300261)\nPenetrance for gene: FAM50A were set to unknown\nReview for gene: FAM50A was set to GREEN\nAdded comment: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference. \r\n\r\nThe authors provide clinical details on 6 affected individuals from 5 families. \r\n\r\nFeatures included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6). \r\n\r\nIn the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam). \r\n\r\nIn affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40).\r\n\r\nMissense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3). \r\n\r\nPrevious studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones). \r\n\r\nImmunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt. \r\n\r\nComplementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish.\r\n\r\nSimilarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins.\r\n\r\nOverall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism. \r\n\r\nSeveral other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.).\r\n\r\nPlease consider inclusion in the ID panel with green rating and epilepsy panel with amber (seizures in individuals from 2 families). \nSources: Literature",
"entity_name": "FAM50A",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:44:29.597472+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.73",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: GBE1 as ready",
"entity_name": "GBE1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:44:29.585460+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.73",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: gbe1 has been classified as Green List (High Evidence).",
"entity_name": "GBE1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:44:27.370774+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.73",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GBE1 were changed from to Glycogen storage disease IV, MIM# 232500",
"entity_name": "GBE1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:44:11.050605+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.72",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: GBE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GBE1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:43:47.996095+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.71",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease IV, MIM# 232500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GBE1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:40:38.780237+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.71",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: GBA as ready",
"entity_name": "GBA",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:40:38.769543+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.71",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: gba has been classified as Green List (High Evidence).",
"entity_name": "GBA",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:40:36.165245+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.71",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GBA were changed from to Gaucher disease",
"entity_name": "GBA",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:40:09.394665+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.70",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GBA were set to ",
"entity_name": "GBA",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:39:48.670517+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.69",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: GBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GBA",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:39:25.369996+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.68",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 32324335; Phenotypes: Gaucher disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GBA",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:36:09.413378+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.68",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: GALT was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GALT",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:35:34.822960+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.67",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GALT were changed from to Galactosemia, MIM# 230400",
"entity_name": "GALT",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:31:43.624084+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.66",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GALT were set to ",
"entity_name": "GALT",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:31:25.992246+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.66",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: GALT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GALT",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:31:02.727703+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.65",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GALT: Rating: GREEN; Mode of pathogenicity: None; Publications: 30693370; Phenotypes: Galactosemia, MIM# 230400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GALT",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:26:14.483163+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.65",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: DHCR7 as ready",
"entity_name": "DHCR7",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:26:14.474216+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.65",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dhcr7 has been classified as Amber List (Moderate Evidence).",
"entity_name": "DHCR7",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:26:11.743625+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.65",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: DHCR7 were changed from to Smith-Lemli-Opitz syndrome, MIM# 270400",
"entity_name": "DHCR7",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:25:48.104626+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.64",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: DHCR7 were set to ",
"entity_name": "DHCR7",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:25:27.633763+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.63",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DHCR7",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:25:10.960803+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.62",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: DHCR7 as Amber List (moderate evidence)",
"entity_name": "DHCR7",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:25:10.950593+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.62",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dhcr7 has been classified as Amber List (Moderate Evidence).",
"entity_name": "DHCR7",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:24:43.235555+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.61",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: DHCR7: Rating: AMBER; Mode of pathogenicity: None; Publications: 20052364; Phenotypes: Smith-Lemli-Opitz syndrome, MIM# 270400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DHCR7",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:22:10.757613+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.61",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: DGUOK as ready",
"entity_name": "DGUOK",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:22:10.710943+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.61",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dguok has been classified as Green List (High Evidence).",
"entity_name": "DGUOK",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:21:56.492936+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.61",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: DGUOK were changed from to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880",
"entity_name": "DGUOK",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:21:35.930830+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.60",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: DGUOK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DGUOK",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:21:12.452793+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: DGUOK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM# 251880; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DGUOK",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:17:00.219779+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CYP7B1 as ready",
"entity_name": "CYP7B1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:17:00.210923+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cyp7b1 has been classified as Green List (High Evidence).",
"entity_name": "CYP7B1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:16:57.294638+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CYP7B1 were changed from to Bile acid synthesis defect, congenital, 3, MIM# 613812",
"entity_name": "CYP7B1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:16:29.985483+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.58",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: CYP7B1 were set to ",
"entity_name": "CYP7B1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:15:59.789642+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.57",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: CYP7B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CYP7B1",
"entity_type": "gene"
},
{
"created": "2020-08-08T18:15:34.534101+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.56",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: CYP7B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31337596, 30366773, 9802883; Phenotypes: Bile acid synthesis defect, congenital, 3, MIM# 613812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CYP7B1",
"entity_type": "gene"
},
{
"created": "2020-08-08T16:00:58.493065+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.56",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: COG7 as ready",
"entity_name": "COG7",
"entity_type": "gene"
},
{
"created": "2020-08-08T16:00:58.482918+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.56",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cog7 has been classified as Green List (High Evidence).",
"entity_name": "COG7",
"entity_type": "gene"
},
{
"created": "2020-08-08T16:00:53.608067+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.56",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: COG7 were changed from to Congenital disorder of glycosylation, type IIe , MIM#608779",
"entity_name": "COG7",
"entity_type": "gene"
},
{
"created": "2020-08-08T16:00:37.297785+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.55",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: COG7 were set to ",
"entity_name": "COG7",
"entity_type": "gene"
},
{
"created": "2020-08-08T16:00:13.452091+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.54",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: COG7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "COG7",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:59:49.357394+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.53",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: COG7: Rating: GREEN; Mode of pathogenicity: None; Publications: 19577670, 17395513, 15107842; Phenotypes: Congenital disorder of glycosylation, type IIe , MIM#608779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "COG7",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:56:01.183648+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.53",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CFTR as ready",
"entity_name": "CFTR",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:56:01.173019+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.53",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cftr has been classified as Amber List (Moderate Evidence).",
"entity_name": "CFTR",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:55:58.833017+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.53",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CFTR were changed from to Cystic fibrosis, MIM# 219700",
"entity_name": "CFTR",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:55:33.830728+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.52",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: CFTR were set to ",
"entity_name": "CFTR",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:55:08.482077+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.51",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: CFTR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CFTR",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:54:48.842400+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.50",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CFTR as Amber List (moderate evidence)",
"entity_name": "CFTR",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:54:48.832536+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.50",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cftr has been classified as Amber List (Moderate Evidence).",
"entity_name": "CFTR",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:54:22.278239+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.49",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: CFTR: Rating: AMBER; Mode of pathogenicity: None; Publications: 25097709; Phenotypes: Cystic fibrosis, MIM# 219700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CFTR",
"entity_type": "gene"
},
{
"created": "2020-08-08T15:50:42.191368+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.49",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: BCS1L as ready",
"entity_name": "BCS1L",
"entity_type": "gene"
}
]
}