HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 221272,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1217",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1215",
"results": [
{
"created": "2021-09-07T14:33:58.390153+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.64",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: glrx5 has been classified as Green List (High Evidence).",
"entity_name": "GLRX5",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:33:56.203378+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.64",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GLRX5 were changed from 616860 Pyridoxine refractory sideroblastic anaemia 3; Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive, 205950; 205950 Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive to Anaemia, sideroblastic, 3, pyridoxine-refractory, MIM# 616860",
"entity_name": "GLRX5",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:33:43.250092+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.63",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GLRX5 were set to 20364084; 25342667; 17485548",
"entity_name": "GLRX5",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:33:25.840421+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.62",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "changed review comment from: Sideroblastic anemia-3 is an autosomal recessive hematologic disorder characterized by onset of anemia in adulthood. Affected individuals show signs of systemic iron overload, and iron chelation therapy may be of clinical benefit. At least three unrelated individuals reported.; to: Sideroblastic anemia-3 is an autosomal recessive hematologic disorder characterized by onset of anaemia in adulthood. Affected individuals show signs of systemic iron overload, and iron chelation therapy may be of clinical benefit. At least three unrelated individuals reported.",
"entity_name": "GLRX5",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:33:00.540230+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.62",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: GIF as ready",
"entity_name": "GIF",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:33:00.530131+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.62",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: gif has been classified as Green List (High Evidence).",
"entity_name": "GIF",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:32:58.440382+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.62",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GIF were changed from 261000 Intrinsic factor deficiency to Intrinsic factor deficiency, MIM# 261000",
"entity_name": "GIF",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:32:49.850455+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.61",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GIF were set to 15738392; 14576042",
"entity_name": "GIF",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:32:35.467081+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.60",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GIF: Rating: GREEN; Mode of pathogenicity: None; Publications: 14695536, 14576042, 15738392; Phenotypes: Intrinsic factor deficiency, MIM# 261000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GIF",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:29:37.439134+10:00",
"panel_name": "Regression",
"panel_id": 206,
"panel_version": "0.371",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: GCLC as ready",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:29:37.422678+10:00",
"panel_name": "Regression",
"panel_id": 206,
"panel_version": "0.371",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: gclc has been classified as Green List (High Evidence).",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:29:34.293294+10:00",
"panel_name": "Regression",
"panel_id": 206,
"panel_version": "0.371",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GCLC were changed from to Haemolytic anaemia due to gamma-glutamylcysteine synthetase deficiency, MIM# 230450",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:29:10.843252+10:00",
"panel_name": "Regression",
"panel_id": 206,
"panel_version": "0.370",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GCLC were set to ",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:28:46.448528+10:00",
"panel_name": "Regression",
"panel_id": 206,
"panel_version": "0.369",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: GCLC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:28:13.908229+10:00",
"panel_name": "Regression",
"panel_id": 206,
"panel_version": "0.368",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GCLC: Rating: GREEN; Mode of pathogenicity: None; Publications: 28571779, 10515893; Phenotypes: Haemolytic anaemia due to gamma-glutamylcysteine synthetase deficiency, MIM# 230450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:25:35.574787+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9095",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: GCLC as ready",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:25:35.565582+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9095",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: gclc has been classified as Green List (High Evidence).",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:24:09.006565+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.60",
"user_name": "Danielle Ariti",
"item_type": "entity",
"text": "reviewed gene: UMPS: Rating: GREEN; Mode of pathogenicity: None; Publications: 9042911, 33489760; Phenotypes: Orotic aciduria MIM# 258900, megaloblastic anaemia, orotic acid crystalluria, ID, immunodeficiencies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "UMPS",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:01:10.694205+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9095",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GCLC were changed from to Haemolytic anaemia due to gamma-glutamylcysteine synthetase deficiency MIM#230450; Disorders of the gamma-glutamyl cycle",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:00:52.987350+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9094",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GCLC were set to ",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:00:21.060290+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9093",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: GCLC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T14:00:00.300370+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9092",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GCLC: Rating: GREEN; Mode of pathogenicity: None; Publications: 10515893, 28571779; Phenotypes: Haemolytic anaemia due to gamma-glutamylcysteine synthetase deficiency, MIM# 230450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T13:57:18.698326+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.60",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: GCLC as ready",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T13:57:18.687826+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.60",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: gclc has been classified as Green List (High Evidence).",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T13:57:16.719916+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.60",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GCLC were changed from Haemolytic anemia due to gamma-glutamylcysteine synthetase deficiency, MIM# 230450 to Haemolytic anaemia due to gamma-glutamylcysteine synthetase deficiency, MIM# 230450",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T13:57:09.357405+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GCLC were changed from 230450 Glutamate-cysteine ligase deficiency; Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency, 230450; Enzyme Disorder; Glutamate-cysteine ligase deficiency; 230450 Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency to Haemolytic anemia due to gamma-glutamylcysteine synthetase deficiency, MIM# 230450",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T13:56:56.644315+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.58",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GCLC were set to 10515893",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T13:56:44.692236+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.57",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GCLC: Rating: GREEN; Mode of pathogenicity: None; Publications: 10515893, 28571779; Phenotypes: Haemolytic anemia due to gamma-glutamylcysteine synthetase deficiency, MIM# 230450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GCLC",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:45:40.578979+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.143",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked STR: FRA7A as ready",
"entity_name": "FRA7A",
"entity_type": "str"
},
{
"created": "2021-09-07T12:45:40.568523+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.143",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Str: fra7a has been classified as Red List (Low Evidence).",
"entity_name": "FRA7A",
"entity_type": "str"
},
{
"created": "2021-09-07T12:45:25.121163+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.143",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "STR: FRA7A was added\nSTR: FRA7A was added to Repeat Disorders. Sources: Literature\nMode of inheritance for STR: FRA7A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for STR: FRA7A were set to 25196122\nPhenotypes for STR: FRA7A were set to Autism spectrum disorder\nReview for STR: FRA7A was set to AMBER\nAdded comment: A de novo occurrence of the 7p11.2 folate-sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to a CGG-repeat expansion mutation (∼450 repeats) in a 5' intron of ZNF713. The expanded allele showed hypermethylation of the adjacent CpG island and reduced ZNF713 expression observed in a proband-derived lymphoblastoid cell line. The probands mother had a pre-mutation with 85 repeats. Controls showed a CGG-repeat range of 5 to 22. In a second family a pre-mutation (66-72) was identified in 3 siblings with ASD and an unaffected father. One of the siblings had mitotic instability. \nSources: Literature",
"entity_name": "FRA7A",
"entity_type": "str"
},
{
"created": "2021-09-07T12:17:26.014154+10:00",
"panel_name": "Deafness_IsolatedAndComplex",
"panel_id": 209,
"panel_version": "1.91",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MAP1B as ready",
"entity_name": "MAP1B",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:17:26.003030+10:00",
"panel_name": "Deafness_IsolatedAndComplex",
"panel_id": 209,
"panel_version": "1.91",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: map1b has been classified as Green List (High Evidence).",
"entity_name": "MAP1B",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:17:20.185532+10:00",
"panel_name": "Deafness_IsolatedAndComplex",
"panel_id": 209,
"panel_version": "1.91",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: MAP1B as Green List (high evidence)",
"entity_name": "MAP1B",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:17:20.174162+10:00",
"panel_name": "Deafness_IsolatedAndComplex",
"panel_id": 209,
"panel_version": "1.91",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: map1b has been classified as Green List (High Evidence).",
"entity_name": "MAP1B",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:16:17.070169+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9092",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PDGFRL as ready",
"entity_name": "PDGFRL",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:16:17.060057+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9092",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pdgfrl has been classified as Red List (Low Evidence).",
"entity_name": "PDGFRL",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:16:06.598585+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9092",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: PDGFRL as Red List (low evidence)",
"entity_name": "PDGFRL",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:16:06.586573+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9092",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pdgfrl has been classified as Red List (Low Evidence).",
"entity_name": "PDGFRL",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:06:14.718529+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.57",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: YARS2 as ready",
"entity_name": "YARS2",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:06:14.709180+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.57",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: yars2 has been classified as Green List (High Evidence).",
"entity_name": "YARS2",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:06:12.023672+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.57",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: YARS2 were changed from 613561 Myopathy, lactic acidosis, and sideroblastic anemia 2; Myopathy, lactic acidosis, and sideroblastic anemia 2, 613561 to Myopathy, lactic acidosis, and sideroblastic anaemia 2 MIM# 613561; sideroblastic anaemia; muscle atrophy; myopathy; lactic acidosis; Hypertrophic cardiomyopathy; Hepatomegaly; Decreased cytochrome C oxidase activity",
"entity_name": "YARS2",
"entity_type": "gene"
},
{
"created": "2021-09-07T12:05:15.571731+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.56",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: YARS2 were set to 23918765; 22504945; 20598274",
"entity_name": "YARS2",
"entity_type": "gene"
},
{
"created": "2021-09-07T11:35:42.329800+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.142",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked STR: VACTERLX as ready",
"entity_name": "VACTERLX",
"entity_type": "str"
},
{
"created": "2021-09-07T11:35:42.320429+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.142",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Str: vacterlx has been classified as Red List (Low Evidence).",
"entity_name": "VACTERLX",
"entity_type": "str"
},
{
"created": "2021-09-07T11:35:28.530811+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.142",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "STR: VACTERLX was added\nSTR: VACTERLX was added to Repeat Disorders. Sources: Literature\nMode of inheritance for STR: VACTERLX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPublications for STR: VACTERLX were set to 20452998; 32639022\nPhenotypes for STR: VACTERLX were set to VACTERL association, X-linked MIM#314390\nReview for STR: VACTERLX was set to RED\nAdded comment: NM_003413.4(ZIC3):c.163GCC[X]\r\nPMID: 20452998 - reports a single case with VACTERL association and an expansion of the poly-Ala tract from 10 to 12 alanines. \r\nPMID: 32639022 - a family with Oculo-auriculo-vertebral spectrum (OAVS) segregates the 11 alanine expansion in affected males\r\nThis polyalanine tract is highly polymorphic in gnomAD v2.1, there are 86 hemizygote 12 alanine expansions present and 65 hemizygotes with the 11 alanine expansion. The 13 polyalanine expansion is also present in 13 hemizygotes. \nSources: Literature",
"entity_name": "VACTERLX",
"entity_type": "str"
},
{
"created": "2021-09-07T11:04:18.910320+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9091",
"user_name": "Michelle Torres",
"item_type": "entity",
"text": "reviewed gene: PDGFRL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown; Current diagnostic: yes",
"entity_name": "PDGFRL",
"entity_type": "gene"
},
{
"created": "2021-09-07T10:54:55.391750+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.141",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked STR: FRA12A as ready",
"entity_name": "FRA12A",
"entity_type": "str"
},
{
"created": "2021-09-07T10:54:55.381536+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.141",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Str: fra12a has been classified as Amber List (Moderate Evidence).",
"entity_name": "FRA12A",
"entity_type": "str"
},
{
"created": "2021-09-07T10:54:51.300086+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.141",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified STR: FRA12A as Amber List (moderate evidence)",
"entity_name": "FRA12A",
"entity_type": "str"
},
{
"created": "2021-09-07T10:54:51.288143+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.141",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Str: fra12a has been classified as Amber List (Moderate Evidence).",
"entity_name": "FRA12A",
"entity_type": "str"
},
{
"created": "2021-09-07T10:54:40.694573+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.140",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "STR: FRA12A was added\nSTR: FRA12A was added to Repeat Disorders. Sources: Literature\nMode of inheritance for STR: FRA12A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for STR: FRA12A were set to 17236128\nPhenotypes for STR: FRA12A were set to Mental retardation, FRA12A type MIM#136630\nReview for STR: FRA12A was set to AMBER\nAdded comment: NM_173602.2:c.-137CGG[X]\r\nAll individuals expressing FRA12A had CGG-repeat expansion. The length of the expanded allele in 3 unaffected FRA12A carriers was 650–850 bp. In the two affected patients from 2 families with FRA12A, the length of the expanded allele was ∼1,050-1,150 bp.\r\n70 controls used to determine the \"normal\" repeat range. \nSources: Literature",
"entity_name": "FRA12A",
"entity_type": "str"
},
{
"created": "2021-09-07T10:45:52.518654+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.55",
"user_name": "Danielle Ariti",
"item_type": "entity",
"text": "reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: None; Publications: 8004674, 30128557, 30800707; Phenotypes: McLeod syndrome with or without chronic granulomatous disease MIM# 300842, absence of red blood cell Kx antigen, weak expression of Kell red blood cell antigens, neuroacanthocytosis (peripheral and central nervous systems), cardiovascular abnormalities, myopathy; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2021-09-07T10:32:01.984110+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.139",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked STR: FRA11A as ready",
"entity_name": "FRA11A",
"entity_type": "str"
},
{
"created": "2021-09-07T10:32:01.969032+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.139",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Str: fra11a has been classified as Red List (Low Evidence).",
"entity_name": "FRA11A",
"entity_type": "str"
},
{
"created": "2021-09-07T10:31:07.079392+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.139",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "STR: FRA11A was added\nSTR: FRA11A was added to Repeat Disorders. Sources: Literature\nMode of inheritance for STR: FRA11A was set to Unknown\nPublications for STR: FRA11A were set to 18160775; 453198\nPhenotypes for STR: FRA11A were set to Intellectual disability\nReview for STR: FRA11A was set to RED\nAdded comment: Expansion of a polymorphic CGG-repeat located at the 5' end of the C11orf80 gene causes expression of the folate-sensitive fragile site FRA11A. The CGG-repeat elongation coincides with hypermethylation of the adjacent CpG island and subsequent transcriptional silencing of the C11orf80 gene. The expansion was identified in the 15-year-old proband with intellectual disability as well as in phenotypically normal members of the family. \nSources: Literature",
"entity_name": "FRA11A",
"entity_type": "str"
},
{
"created": "2021-09-07T09:56:13.328361+10:00",
"panel_name": "Red cell disorders",
"panel_id": 3366,
"panel_version": "0.55",
"user_name": "Danielle Ariti",
"item_type": "entity",
"text": "reviewed gene: YARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24430573, 24344687; Phenotypes: Myopathy, lactic acidosis, and sideroblastic anaemia 2 MIM# 613561, sideroblastic anaemia, muscle atrophy, myopathy, lactic acidosis, Hypertrophic cardiomyopathy, Hepatomegaly, Decreased cytochrome C oxidase activity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "YARS2",
"entity_type": "gene"
},
{
"created": "2021-09-07T09:43:05.727408+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.138",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked STR: TOF as ready",
"entity_name": "TOF",
"entity_type": "str"
},
{
"created": "2021-09-07T09:43:05.711699+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.138",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Str: tof has been classified as Green List (High Evidence).",
"entity_name": "TOF",
"entity_type": "str"
},
{
"created": "2021-09-07T09:43:01.737476+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.138",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified STR: TOF as Green List (high evidence)",
"entity_name": "TOF",
"entity_type": "str"
},
{
"created": "2021-09-07T09:43:01.726471+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.138",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Str: tof has been classified as Green List (High Evidence).",
"entity_name": "TOF",
"entity_type": "str"
},
{
"created": "2021-09-07T09:42:50.003569+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.137",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "STR: TOF was added\nSTR: TOF was added to Repeat Disorders. Sources: Literature\nMode of inheritance for STR: TOF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for STR: TOF were set to 19948535; 11748311\nPhenotypes for STR: TOF were set to Tetralogy of Fallot MIM#187500\nReview for STR: TOF was set to GREEN\nSTR: TOF was marked as clinically relevant\nAdded comment: Poly-alanine tract expansion. In vitro functional assays demonstrated the expansion lead to protein aggregation in cells. Two unrelated cases reported with 25 repeats, one case with isolated interrupted aortic arch and one case with scoliosis, facial asymmetry, upslanting\r\npalpebral fissures, absent PV, isolated left pulmonary artery (expected de novo - excluded in mother and father not available for testing). Other variant types cause disease in this gene. \nSources: Literature",
"entity_name": "TOF",
"entity_type": "str"
},
{
"created": "2021-09-07T09:22:47.375216+10:00",
"panel_name": "Deafness_IsolatedAndComplex",
"panel_id": 209,
"panel_version": "1.90",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: MAP1B was added\ngene: MAP1B was added to Deafness_IsolatedAndComplex. Sources: Literature\nMode of inheritance for gene: MAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: MAP1B were set to PMID: 33268592\nPhenotypes for gene: MAP1B were set to Periventricular nodular heterotopia 9 MIM#618918; sensorineural hearing loss\nReview for gene: MAP1B was set to GREEN\nAdded comment: PMID: 33268592 - three unrelated patients with heterozygous missense variants and nonsyndromic sensorineural hearing loss. Functional studies on one missense show reduced protein expression and less phosphorylation. \r\nVariant correction via CRISPR rescued cell dysfunction, and K/O mice show hearing loss \nSources: Literature",
"entity_name": "MAP1B",
"entity_type": "gene"
},
{
"created": "2021-09-07T09:08:21.143829+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.136",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked STR: FRAXF as ready",
"entity_name": "FRAXF",
"entity_type": "str"
},
{
"created": "2021-09-07T09:08:21.135200+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.136",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Str: fraxf has been classified as Red List (Low Evidence).",
"entity_name": "FRAXF",
"entity_type": "str"
},
{
"created": "2021-09-07T09:08:12.924704+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.136",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "STR: FRAXF was added\nSTR: FRAXF was added to Repeat Disorders. Sources: Literature\nMode of inheritance for STR: FRAXF was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPublications for STR: FRAXF were set to 7874164; 10094554; 8651274\nPhenotypes for STR: FRAXF were set to Intellectual disability\nReview for STR: FRAXF was set to RED\nAdded comment: FRAXF is a folate-sensitive fragile site, where expansion was identified in a male with developmental delay. However, further studies found that expression of the fragile site through expansion is not associated with a disease phenotype. \nSources: Literature",
"entity_name": "FRAXF",
"entity_type": "str"
},
{
"created": "2021-09-06T20:34:23.338299+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4106",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: UBE2U as ready",
"entity_name": "UBE2U",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:34:23.327847+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4106",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ube2u has been classified as Red List (Low Evidence).",
"entity_name": "UBE2U",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:34:17.799534+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4106",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: UBE2U as Red List (low evidence)",
"entity_name": "UBE2U",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:34:17.789759+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4106",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ube2u has been classified as Red List (Low Evidence).",
"entity_name": "UBE2U",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:33:47.151426+10:00",
"panel_name": "Cataract",
"panel_id": 66,
"panel_version": "0.287",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: UBE2U as ready",
"entity_name": "UBE2U",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:33:47.138469+10:00",
"panel_name": "Cataract",
"panel_id": 66,
"panel_version": "0.287",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ube2u has been classified as Red List (Low Evidence).",
"entity_name": "UBE2U",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:33:41.755242+10:00",
"panel_name": "Cataract",
"panel_id": 66,
"panel_version": "0.287",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: UBE2U as Red List (low evidence)",
"entity_name": "UBE2U",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:33:41.744815+10:00",
"panel_name": "Cataract",
"panel_id": 66,
"panel_version": "0.287",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ube2u has been classified as Red List (Low Evidence).",
"entity_name": "UBE2U",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:32:05.922313+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9091",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: IFIH1 as ready",
"entity_name": "IFIH1",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:32:05.912677+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9091",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ifih1 has been classified as Green List (High Evidence).",
"entity_name": "IFIH1",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:31:57.096156+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9091",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: IFIH1 were changed from to Aicardi-Goutieres syndrome 7, MIM#615846; Early-onset Inflammatory Bowel Disease",
"entity_name": "IFIH1",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:31:33.477429+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9090",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: IFIH1 were set to ",
"entity_name": "IFIH1",
"entity_type": "gene"
},
{
"created": "2021-09-06T20:31:14.619241+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9089",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: IFIH1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal",
"entity_name": "IFIH1",
"entity_type": "gene"
},
{
"created": "2021-09-06T18:42:56.024884+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1192",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PRICKLE2 as ready",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T18:42:56.015122+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1192",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: prickle2 has been classified as Green List (High Evidence).",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T18:42:13.824182+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1192",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: PRICKLE2 as Green List (high evidence)",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T18:42:13.811060+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1192",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: prickle2 has been classified as Green List (High Evidence).",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T18:35:18.114581+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1191",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: PRICKLE2 was added\ngene: PRICKLE2 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: PRICKLE2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: PRICKLE2 were set to 34092786\nPhenotypes for gene: PRICKLE2 were set to Neurodevelopmental disorder; global developmental delay; behavioural difficulties ± epilepsy; autistic features; attention deficit hyperactive disorder; psychiatric symptoms\nReview for gene: PRICKLE2 was set to GREEN\nAdded comment: Six subjects from four unrelated families with neurodevelopmental delay, behavioural difficulties and epilepsy had heterozygous variants, either de novo or segregating with disease. Two missense were de novo, c.122 C>T; p.(Pro41Leu) and c.680C>G; p.(Thr227Arg); one nonsense variant was de novo (c.214 C>T; p.(Arg72*); and one frameshift variant segregated with the disorder in three affected females (c.1286_1287delGT; p.(Ser429Thrfs*56)). Loss-of-function (homozygous) variants have been shown to cause seizures in flies; and both heterozygous and homozygous mice have shown behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility (PMID: 21276947). \nSources: Literature",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T18:33:39.984550+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4105",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PRICKLE2 as ready",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T18:33:39.959643+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4105",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: prickle2 has been classified as Green List (High Evidence).",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T17:43:09.736991+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.135",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified STR: FRA11B as Red List (low evidence)",
"entity_name": "FRA11B",
"entity_type": "str"
},
{
"created": "2021-09-06T17:43:09.731565+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.135",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Added comment: Comment on list classification: Low evidence of clinical relevance of expression of the fragile site.",
"entity_name": "FRA11B",
"entity_type": "str"
},
{
"created": "2021-09-06T17:43:09.704094+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.135",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Str: fra11b has been classified as Red List (Low Evidence).",
"entity_name": "FRA11B",
"entity_type": "str"
},
{
"created": "2021-09-06T17:41:38.559519+10:00",
"panel_name": "Repeat Disorders",
"panel_id": 3597,
"panel_version": "0.134",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "STR: FRA11B was added\nSTR: FRA11B was added to Repeat Disorders. Sources: Literature\nMode of inheritance for STR: FRA11B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for STR: FRA11B were set to 7881408; 7603564; 9508241; 9927483; 10767345; 11076037; 19267933\nPhenotypes for STR: FRA11B were set to Jacobsen syndrome MIM#147791\nReview for STR: FRA11B was set to AMBER\nAdded comment: FRA11B is a rare folate sensitive fragile site caused by expansion of (CCG)n in the 5'UTR of CBL, and hypermethylation of adjacent CpG islands. There are commonly 11 repeats. The pre-mutation ranges from 80-100, while >100 leads to expression of the fragile site. Two cases of Jacobsen (llq-) syndrome, which is the clinical presentation of the loss of part of the long arm of chromosome 11, have been associated with the FRA11B repeat expansion (expected breakpoint). The estimated prevalence of the FRA11B expansion is 1 in 5,000, which the estimated prevalence of Jacobsen syndrome is <1 in 100,000. \nSources: Literature",
"entity_name": "FRA11B",
"entity_type": "str"
},
{
"created": "2021-09-06T17:36:25.739882+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4105",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PRICKLE2 as ready",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T17:36:25.722321+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4105",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: prickle2 has been classified as Green List (High Evidence).",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T17:36:10.108215+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4105",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: PRICKLE2 as Green List (high evidence)",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T17:36:10.098942+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4105",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: prickle2 has been classified as Green List (High Evidence).",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T16:19:48.752254+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4104",
"user_name": "Hazel Phillimore",
"item_type": "entity",
"text": "gene: PRICKLE2 was added\ngene: PRICKLE2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: PRICKLE2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: PRICKLE2 were set to PMID: 34092786\nPhenotypes for gene: PRICKLE2 were set to Neurodevelopmental disorder; global developmental delay; behavioural difficulties ± epilepsy; autistic features; attention deficit hyperactive disorder; psychiatric symptoms\nReview for gene: PRICKLE2 was set to GREEN\nAdded comment: Six subjects from four unrelated families with neurodevelopmental delay, behavioural difficulties and epilepsy had heterozygous variants, either de novo or segregating with disease. \r\n\r\nTwo missense were de novo, c.122 C>T; p.(Pro41Leu) and c.680C>G; p.(Thr227Arg); one nonsense variant was de novo (c.214 C>T; p.(Arg72*); and one frameshift variant segregated with the disorder in three affected females (c.1286_1287delGT; p.(Ser429Thrfs*56)). \r\n\r\nLoss-of-function (homozygous) variants have been shown to cause seizures in flies; and both heterozygous and homozygous mice have shown behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility (PMID: 21276947). \nSources: Literature",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T16:18:36.553210+10:00",
"panel_name": "Inflammatory bowel disease",
"panel_id": 123,
"panel_version": "0.59",
"user_name": "Sarah Pantaleo",
"item_type": "entity",
"text": "changed review comment from: Rare, likely loss-of-functions IFIH1 variants identified in eight patients with Very Early Onset Inflammatory Bowel Disease (VEOIBD) with VEOIBD from a combined cohort of 42 children. One homozygous truncating variant in a neonate from a consanguineous family, seven carriers of LoF variants (three of whom also have a second hypomorphic missense variant). Luciferase reporter assays employed to assess MDA5 activity (encoded by IFIH1). In three cases, the functional studies demonstrated that the second missense variant either did not affect protein function or was in cis with the LoF variant. \nSources: Literature; to: IFIH1 encodes MDA5, a key cystolic sensor for viral nucleic acids. Rare, likely loss-of-functions IFIH1 variants identified in eight independent probands with Very Early Onset Inflammatory Bowel Disease (VEOIBD) from a combined cohort of 42 children. IFIH1 variants were significantly enriched in children with VEOIBD as compared to controls (p=0.007).\r\nIn one case of neonatal-onset IBD, a homozygous truncating variant was identified. There were seven carriers of LoF variants identified (range of onset 6 months to 6 years of age). In three of these cases, a second hypomorphic missense variant was identified. \r\nLuciferase reporter assays were employed to assess MDA5 activity. In some cases, the second missense variant was either proven to not affect protein function or was in cis with the LoF variant.\r\nComplete and partial MDA5 deficiency is associated with VEOIBD with variable penetrance and expressivity, suggesting a role for impaired intestinal viral sensing in IBD pathogenesis.\r\nSources: Literature",
"entity_name": "IFIH1",
"entity_type": "gene"
},
{
"created": "2021-09-06T16:17:17.356404+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9088",
"user_name": "Sarah Pantaleo",
"item_type": "entity",
"text": "changed review comment from: Rare, likely loss-of-functions IFIH1 variants identified in eight independent probands with Very Early Onset Inflammatory Bowel Disease (VEOIBD) from a combined cohort of 42 children. IFIH1 variants were significantly enriched in children with VEOIBD as compared to controls (p=0.007).\r\nIn one case of neonatal-onset IBD, a homozygous truncating variant was identified. seven carriers of LoF variants (three of whom have a second hypomorphic missense variant). Luciferase reporter assays employed to assess MDA5 activity (encoded by IFIH1). In three cases, the functional studies demonstrated that the second missense variant either did not affect protein function or was in cis with the LoF variant.; to: IFIH1 encodes MDA5, a key cystolic sensor for viral nucleic acids. Rare, likely loss-of-functions IFIH1 variants identified in eight independent probands with Very Early Onset Inflammatory Bowel Disease (VEOIBD) from a combined cohort of 42 children. IFIH1 variants were significantly enriched in children with VEOIBD as compared to controls (p=0.007).\r\nIn one case of neonatal-onset IBD, a homozygous truncating variant was identified. There were seven carriers of LoF variants identified (range of onset 6 months to 6 years of age). In three of these cases, a second hypomorphic missense variant was identified. \r\nLuciferase reporter assays were employed to assess MDA5 activity. In some cases, the second missense variant was either proven to not affect protein function or was in cis with the LoF variant.\r\nComplete and partial MDA5 deficiency is associated with VEOIBD with variable penetrance and expressivity, suggesting a role for impaired intestinal viral sensing in IBD pathogenesis.",
"entity_name": "IFIH1",
"entity_type": "gene"
},
{
"created": "2021-09-06T16:12:29.076045+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9088",
"user_name": "Sarah Pantaleo",
"item_type": "entity",
"text": "changed review comment from: Rare, likely loss-of-functions IFIH1 variants identified in eight patients with Very Early Onset Inflammatory Bowel Disease (VEOIBD) with VEOIBD from a combined cohort of 42 children. One homozygous truncating variant in a neonate from a consanguineous family, seven carriers of LoF variants (three of whom also have a second hypomorphic missense variant). Luciferase reporter assays employed to assess MDA5 activity (encoded by IFIH1). In three cases, the functional studies demonstrated that the second missense variant either did not affect protein function or was in cis with the LoF variant.; to: Rare, likely loss-of-functions IFIH1 variants identified in eight independent probands with Very Early Onset Inflammatory Bowel Disease (VEOIBD) from a combined cohort of 42 children. IFIH1 variants were significantly enriched in children with VEOIBD as compared to controls (p=0.007).\r\nIn one case of neonatal-onset IBD, a homozygous truncating variant was identified. seven carriers of LoF variants (three of whom have a second hypomorphic missense variant). Luciferase reporter assays employed to assess MDA5 activity (encoded by IFIH1). In three cases, the functional studies demonstrated that the second missense variant either did not affect protein function or was in cis with the LoF variant.",
"entity_name": "IFIH1",
"entity_type": "gene"
},
{
"created": "2021-09-06T16:11:31.201789+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.9088",
"user_name": "Hazel Phillimore",
"item_type": "entity",
"text": "changed review comment from: Six subjects from four unrelated families with heterozygous variants (two de novo missense (c.122 C>T; p.(Pro41Leu) and c.680C>G; p.(Thr227Arg)), one de novo nonsense variant (c.214 C>T; p.(Arg72*) and one frameshift variant (c.1286_1287delGT; p.(Ser429Thrfs*56)) which segregated with the disease in three affected females. \r\n\r\nLoss-of-function (homozygous) variants cause seizures in flies, and both heterozygous and homozygous mice showed behavioral abnormalities including altered social interaction, learning abnormalities, and behavioural inflexibility. PubMed: 21276947.; to: Six subjects from four unrelated families with neurodevelopmental delay, behavioural difficulties and epilepsy had heterozygous variants, either de novo or segregating with disease. \r\nTwo missense were de novo, c.122 C>T; p.(Pro41Leu) and c.680C>G; p.(Thr227Arg); one nonsense variant was de novo (c.214 C>T; p.(Arg72*); and one frameshift variant segregated with the disorder in three affected females (c.1286_1287delGT; p.(Ser429Thrfs*56)). \r\n\r\nLoss-of-function (homozygous) variants have been shown to cause seizures in flies; and both heterozygous and homozygous mice have shown behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility (PubMed: 21276947).\r\n",
"entity_name": "PRICKLE2",
"entity_type": "gene"
},
{
"created": "2021-09-06T16:08:30.758448+10:00",
"panel_name": "Inflammatory bowel disease",
"panel_id": 123,
"panel_version": "0.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: IFIH1 as ready",
"entity_name": "IFIH1",
"entity_type": "gene"
}
]
}