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{
"count": 220463,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=963",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=961",
"results": [
{
"created": "2022-02-28T18:01:26.604917+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4324",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: exoc7 has been classified as Green List (High Evidence).",
"entity_name": "EXOC7",
"entity_type": "gene"
},
{
"created": "2022-02-28T18:01:13.873475+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4324",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: EXOC7 were set to ",
"entity_name": "EXOC7",
"entity_type": "gene"
},
{
"created": "2022-02-28T18:00:50.628060+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4323",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: EXOC7 as Green List (high evidence)",
"entity_name": "EXOC7",
"entity_type": "gene"
},
{
"created": "2022-02-28T18:00:50.612914+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4323",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: exoc7 has been classified as Green List (High Evidence).",
"entity_name": "EXOC7",
"entity_type": "gene"
},
{
"created": "2022-02-28T18:00:28.546035+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4322",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: EXOC7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32103185; Phenotypes: Neurodevelopmental disorder with seizures and brain atrophy MIM#619072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "EXOC7",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:59:12.220348+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4322",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: DYNC1I2 as ready",
"entity_name": "DYNC1I2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:59:12.207049+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4322",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dync1i2 has been classified as Green List (High Evidence).",
"entity_name": "DYNC1I2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:59:05.547365+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4322",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: DYNC1I2 as Green List (high evidence)",
"entity_name": "DYNC1I2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:59:05.527122+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4322",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dync1i2 has been classified as Green List (High Evidence).",
"entity_name": "DYNC1I2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:58:34.980913+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4321",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: FIBP as ready",
"entity_name": "FIBP",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:58:34.971203+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4321",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fibp has been classified as Amber List (Moderate Evidence).",
"entity_name": "FIBP",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:58:30.108615+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4321",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: FIBP as Amber List (moderate evidence)",
"entity_name": "FIBP",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:58:30.096496+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4321",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fibp has been classified as Amber List (Moderate Evidence).",
"entity_name": "FIBP",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:57:57.889865+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4320",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: B3GNT2 as ready",
"entity_name": "B3GNT2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:57:57.877094+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4320",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: b3gnt2 has been classified as Amber List (Moderate Evidence).",
"entity_name": "B3GNT2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:56:07.114759+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4320",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: B3GNT2 as Amber List (moderate evidence)",
"entity_name": "B3GNT2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:56:07.103899+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4320",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: b3gnt2 has been classified as Amber List (Moderate Evidence).",
"entity_name": "B3GNT2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:55:32.315069+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4319",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CTNNA2 as ready",
"entity_name": "CTNNA2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:55:32.303014+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4319",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ctnna2 has been classified as Green List (High Evidence).",
"entity_name": "CTNNA2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:55:26.053456+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4319",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CTNNA2 as Green List (high evidence)",
"entity_name": "CTNNA2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:55:26.035938+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4319",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ctnna2 has been classified as Green List (High Evidence).",
"entity_name": "CTNNA2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:55:08.179374+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4318",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: TUBGCP2 as Green List (high evidence)",
"entity_name": "TUBGCP2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:55:08.169119+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4318",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: tubgcp2 has been classified as Green List (High Evidence).",
"entity_name": "TUBGCP2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:54:58.483051+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4317",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: DICER1 as ready",
"entity_name": "DICER1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:54:58.471549+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4317",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dicer1 has been classified as Green List (High Evidence).",
"entity_name": "DICER1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:54:58.203462+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4317",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: TUBGCP2 was added\ngene: TUBGCP2 was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TUBGCP2 were set to PMID: 31630790\nPhenotypes for gene: TUBGCP2 were set to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM #\t618737\nReview for gene: TUBGCP2 was set to GREEN\nAdded comment: Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures (PAMDDFS) is an autosomal recessive neurologic disorder characterized by progressive microcephaly associated with abnormal facial features, hypotonia, and variable global developmental delay with impaired intellectual development. Brain imaging shows variable malformation of cortical development on the lissencephaly spectrum, mainly pachygyria and thin corpus callosum.\r\n\r\n4 unrelated patients with homozygous or compound heterozygous mutations in the TUBGCP2 gene, found by WES and segregated with the disorder in all families. Functional studies of the variants were not performed, but analysis of patient fibroblasts derived from the patient with a splice site mutation demonstrated the production of several abnormal transcripts that were predicted to result in a loss of function. \nSources: Expert list",
"entity_name": "TUBGCP2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:54:16.453779+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4316",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: DICER1 as Green List (high evidence)",
"entity_name": "DICER1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:54:16.441144+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4316",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dicer1 has been classified as Green List (High Evidence).",
"entity_name": "DICER1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:53:21.661551+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4315",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: COPB2 as ready",
"entity_name": "COPB2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:53:21.649919+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4315",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: copb2 has been classified as Red List (Low Evidence).",
"entity_name": "COPB2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:53:16.837490+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4315",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: COPB2 as Red List (low evidence)",
"entity_name": "COPB2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:53:16.826991+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4315",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: copb2 has been classified as Red List (Low Evidence).",
"entity_name": "COPB2",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:52:43.751068+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: ARF1 as ready",
"entity_name": "ARF1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:52:43.730276+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: arf1 has been classified as Green List (High Evidence).",
"entity_name": "ARF1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:52:38.215628+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: ARF1 as Green List (high evidence)",
"entity_name": "ARF1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:52:38.205882+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: arf1 has been classified as Green List (High Evidence).",
"entity_name": "ARF1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:52:15.758769+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4313",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: ARF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Periventricular nodular heterotopia 8 (MIM#618185); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "ARF1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:51:23.414973+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4313",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: ATXN2L as ready",
"entity_name": "ATXN2L",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:51:23.403680+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4313",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: atxn2l has been classified as Amber List (Moderate Evidence).",
"entity_name": "ATXN2L",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:51:17.974817+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4313",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: ATXN2L as Amber List (moderate evidence)",
"entity_name": "ATXN2L",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:51:17.964321+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4313",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: atxn2l has been classified as Amber List (Moderate Evidence).",
"entity_name": "ATXN2L",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:50.868447+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4312",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: VPS4A as Green List (high evidence)",
"entity_name": "VPS4A",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:50.858616+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4312",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: vps4a has been classified as Green List (High Evidence).",
"entity_name": "VPS4A",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:42.019128+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4311",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: COPB1 as ready",
"entity_name": "COPB1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:42.006824+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4311",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: copb1 has been classified as Red List (Low Evidence).",
"entity_name": "COPB1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:38.225118+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4311",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: VPS4A was added\ngene: VPS4A was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: VPS4A were set to PMID: 33186543; 33186545\nPhenotypes for gene: VPS4A were set to CIMDAG syndrome MIM# 619273\nReview for gene: VPS4A was set to GREEN\nAdded comment: CIMDAG syndrome is a multisystemic disorder characterized by severely impaired psychomotor development and hematologic abnormalities apparent from early infancy. Affected individuals show poor overall growth with microcephaly, impaired intellectual development, poor or absent speech, poor eye contact, and motor problems, such as inability to walk, hypotonia, and spasticity. Brain imaging typically shows cerebral and cerebellar atrophy, thin corpus callosum, and delayed myelination. The associated hematologic abnormalities are variable, but are mostly consistent with congenital dyserythropoietic anemia. Eight unrelated patients with de novo heterozygous missense mutations in the VPS4A gene. \nSources: Expert list",
"entity_name": "VPS4A",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:36.210913+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4311",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: COPB1 as Red List (low evidence)",
"entity_name": "COPB1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:36.198829+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4311",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: copb1 has been classified as Red List (Low Evidence).",
"entity_name": "COPB1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:10.936839+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4310",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CHKA as ready",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:10.921647+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4310",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: chka has been classified as Red List (Low Evidence).",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:04.669561+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4310",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CHKA as Red List (low evidence)",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:50:04.652823+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4310",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: chka has been classified as Red List (Low Evidence).",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:49:37.269397+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4309",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CENPE as ready",
"entity_name": "CENPE",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:49:37.256286+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4309",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cenpe has been classified as Red List (Low Evidence).",
"entity_name": "CENPE",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:49:30.553475+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4309",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CENPE as Red List (low evidence)",
"entity_name": "CENPE",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:49:30.541159+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4309",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cenpe has been classified as Red List (Low Evidence).",
"entity_name": "CENPE",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:48:57.992191+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4308",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CDK6 as ready",
"entity_name": "CDK6",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:48:57.982856+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4308",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cdk6 has been classified as Amber List (Moderate Evidence).",
"entity_name": "CDK6",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:48:52.258902+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4308",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CDK6 as Amber List (moderate evidence)",
"entity_name": "CDK6",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:48:52.246303+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4308",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cdk6 has been classified as Amber List (Moderate Evidence).",
"entity_name": "CDK6",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:48:25.071794+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4307",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CCDC88A as ready",
"entity_name": "CCDC88A",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:48:25.060015+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4307",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ccdc88a has been classified as Amber List (Moderate Evidence).",
"entity_name": "CCDC88A",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:48:19.969861+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4307",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CCDC88A as Amber List (moderate evidence)",
"entity_name": "CCDC88A",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:48:19.960894+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4307",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ccdc88a has been classified as Amber List (Moderate Evidence).",
"entity_name": "CCDC88A",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:47:34.087711+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4306",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: VPS50 as Amber List (moderate evidence)",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:47:34.066382+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4306",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:47:21.790880+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4305",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: VPS50 was added\ngene: VPS50 was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: VPS50 were set to PMID: 34037727\nPhenotypes for gene: VPS50 were set to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685\nReview for gene: VPS50 was set to AMBER\nAdded comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants. Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)). VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor. As discussed by Schneeberger et al (refs provided in text): - VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development. - Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality. Studies performed by Schneeberger et al included: - Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del). - Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels. - Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts. - Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function. As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term \"GARP and/or EARP deficiency disorders\". There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes. \nSources: Expert list",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:45:21.176799+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4304",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: VPS51 as Amber List (moderate evidence)",
"entity_name": "VPS51",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:45:21.164629+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4304",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: vps51 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS51",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:45:11.436875+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4303",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: VPS51 was added\ngene: VPS51 was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: VPS51 were set to PMID: 30624672; 31207318\nPhenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606\nReview for gene: VPS51 was set to AMBER\nAdded comment: Pontocerebellar hypoplasia type 13 (PCH13) is an autosomal recessive disorder characterized by global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment. Two families reported with bi-allelic variants in this gene. \nSources: Expert list",
"entity_name": "VPS51",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:41:11.132947+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4302",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: WDR37 as Green List (high evidence)",
"entity_name": "WDR37",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:41:11.121650+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4302",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: wdr37 has been classified as Green List (High Evidence).",
"entity_name": "WDR37",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:40:55.424760+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4301",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: WDR37 was added\ngene: WDR37 was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: WDR37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: WDR37 were set to PMID: 31327508, 31327510\nPhenotypes for gene: WDR37 were set to Neurooculocardiogenitourinary syndrome MIM#618652\nReview for gene: WDR37 was set to GREEN\nAdded comment: Neurooculocardiogenitourinary syndrome (NOCGUS) is a multisystem disorder characterized by poor growth and anomalies of the ocular, craniofacial, neurologic, cardiovascular, genitourinary, skeletal, and gastrointestinal systems. Lethality before 2 years of age has been observed. Nine unrelated patients reported with de novo missense mutations in the WDR37 gene. \nSources: Expert list",
"entity_name": "WDR37",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:37:03.079782+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4300",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: WDR4 as Green List (high evidence)",
"entity_name": "WDR4",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:37:03.069575+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4300",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: wdr4 has been classified as Green List (High Evidence).",
"entity_name": "WDR4",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:36:52.346704+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4299",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: WDR4 was added\ngene: WDR4 was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: WDR4 were set to PubMed: 26416026; 28617965\nPhenotypes for gene: WDR4 were set to Microcephaly, growth deficiency, seizures, and brain malformations, OMIM # 618346\nReview for gene: WDR4 was set to GREEN\nAdded comment: Microcephaly, growth deficiency, seizures, and brain malformations (MIGSB) is a severe autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth deficiency with severe microcephaly, and poor or absent psychomotor development. Additional features include optic atrophy, early-onset seizures, dysmorphic facial features, and brain malformations, such as partial agenesis of the corpus callosum and simplified gyration.\r\n\r\nBiallelic variants in the WDR4 gene reported in 4 patients from 3 unrelated families. Studies of patient cells in one family and modeling of the corresponding mutation in yeast showed that the mutation caused a significant reduction in m(7)G46 methylation of specific tRNAs species, particularly at higher temperatures. This was associated with a growth defect in yeast, thus offering a potential mechanism for the growth defects observed in patients with the mutation. The findings suggested that abnormal tRNA modification is a major contributor to disease pathogenesis. \nSources: Literature",
"entity_name": "WDR4",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:29:01.902122+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4298",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: YIPF5 as Green List (high evidence)",
"entity_name": "YIPF5",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:29:01.887330+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4298",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: yipf5 has been classified as Green List (High Evidence).",
"entity_name": "YIPF5",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:28:51.818275+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4297",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: YIPF5 was added\ngene: YIPF5 was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: YIPF5 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: YIPF5 were set to PMID: 33164986\nPhenotypes for gene: YIPF5 were set to Microcephaly, epilepsy, and diabetes syndrome 2 , MIM#619278\nReview for gene: YIPF5 was set to GREEN\nAdded comment: 6 patients from 5 consanguineous families who had microcephaly, epilepsy, and diabetes syndrome (MEDS). All had severe microcephaly (standard deviation of -6.2); epilepsy diagnosed at ages ranging from 1 to 7 months; and neonatal/early-onset diabetes. All patients had low birth weight consistent with reduced insulin secretion in utero. \nSources: Expert list",
"entity_name": "YIPF5",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:26:54.737615+11:00",
"panel_name": "Disorders of immune dysregulation",
"panel_id": 229,
"panel_version": "0.106",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Publications for gene: AP3D1 were set to 26744459; 9697856",
"entity_name": "AP3D1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:26:24.044735+11:00",
"panel_name": "Disorders of immune dysregulation",
"panel_id": 229,
"panel_version": "0.105",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: AP3D1 as Green List (high evidence)",
"entity_name": "AP3D1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:26:24.033937+11:00",
"panel_name": "Disorders of immune dysregulation",
"panel_id": 229,
"panel_version": "0.105",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: ap3d1 has been classified as Green List (High Evidence).",
"entity_name": "AP3D1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:26:12.801084+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4296",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: YIF1B as Green List (high evidence)",
"entity_name": "YIF1B",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:26:12.790203+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4296",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: yif1b has been classified as Green List (High Evidence).",
"entity_name": "YIF1B",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:25:50.305601+11:00",
"panel_name": "Disorders of immune dysregulation",
"panel_id": 229,
"panel_version": "0.104",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "reviewed gene: AP3D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30472485, 9697856, 26744459; Phenotypes: Hermansky-Pudlak syndrome 10, MIM# 617050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "AP3D1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:25:22.681125+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4295",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: YIF1B was added\ngene: YIF1B was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: YIF1B were set to PMID: 32006098; 26077767\nPhenotypes for gene: YIF1B were set to Kaya-Barakat-Masson syndrome, MIM# 619125\nReview for gene: YIF1B was set to GREEN\nAdded comment: Kaya-Barakat-Masson syndrome (KABAMAS) is a severe autosomal recessive neurodevelopmental disorder characterized by profoundly impaired global development, peripheral spasticity, dystonia, impaired intellectual development with absent speech, poor eye contact, and feeding difficulties, resulting in poor overall growth, sometimes with microcephaly. Additional more variable features include early-onset seizures, ocular anomalies, foot deformities, and nonspecific brain imaging findings, such as thin corpus callosum and cerebral, cerebellar, or pontine atrophy. Some patients may die in infancy or early childhood.\r\n\r\n6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function. \nSources: Expert list",
"entity_name": "YIF1B",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:23:04.056768+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4294",
"user_name": "Krithika Murali",
"item_type": "entity",
"text": "gene: NFIB was added\ngene: NFIB was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: NFIB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: NFIB were set to 30388402; 33130023; 32902921\nPhenotypes for gene: NFIB were set to Macrocephaly, acquired, with impaired intellectual development - MIM#618286\nReview for gene: NFIB was set to GREEN\nAdded comment: NFIB haploinsufficiency associated with syndromic ID. Macrocephaly and corpus callosum anomalies are recurrent phenotypic features. OMIM notes macrocephaly postnatal in onset, but review of published cases shows some instances of relative macrocephaly at birth. Also corpus callosal anomalies - agenesis and dysgenesis, noted on MRI-B in childhood but possibility of detecting this antenatally in future cases. 2 unrelated individuals reported with minor cardiac anomalies also.\r\n\r\n---\r\n\r\nOMIM notes macrocephaly postnatal in onset. PMID: 30388402 - 18 individuals reported, of whom 11 had deletions of this gene and the rest had SNVs. Relative macrocephaly noted based on growth parameters in 4 individuals (e.g. x1 male with BW 22nd centile and HC 99th centile in an apparently uncomplicated pregnancy) - macrocephaly became more pronounced with age. In addition, 2 individuals had congenital cardiac anomalies (x1 small VSD and x1 narrow pulmonary artery) and 2 individuals had complete agenesis of the corpus callosum.\r\n\r\n33130023 - Report one affected individual. Birth weight was 4.13 kg (Z-score 1.50, 93rd percentile), length was 52 cm (Z-score 1.12, 87th percentile) and his head circumference was 37 cm (Z-score 2.00, 98th percentile). MRI-B at 12 months confirmed agenesis of the corpus callosum\r\n\r\n32902921 - report one patient with normal antenatal history, no birth HC provided, macrocephaly noted at 7 months. MRI-B showed mild dysgensis of the corpus callosum age 5. 2nd unrelated patient's birth weight 3.43 kg(57th centile,Zscore 0.17), length 52.8 cm (94th centile, Zscore1.54), and OFC 37.5 cm (99th centile,Zscore 2.39). MRI-B age 5 showed dysgenesis of the corpus callosum. \nSources: Literature",
"entity_name": "NFIB",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:22:32.610104+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4294",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: YRDC as Green List (high evidence)",
"entity_name": "YRDC",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:22:32.600069+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4294",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: yrdc has been classified as Green List (High Evidence).",
"entity_name": "YRDC",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:22:10.662010+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4293",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: YRDC was added\ngene: YRDC was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: YRDC was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: YRDC were set to PMID: 31481669, 34545459\nPhenotypes for gene: YRDC were set to Galloway-Mowat syndrome 10, OMIM # 619609\nReview for gene: YRDC was set to GREEN\nAdded comment: Galloway-Mowat syndrome-10 (GAMOS10) is a severe autosomal recessive disorder characterized by onset of symptoms soon after birth. Affected individuals have progressive renal dysfunction with proteinuria associated with diffuse mesangial sclerosis (DMS) on renal biopsy. Other features include global developmental delay, microcephaly, hypothyroidism, arachnodactyly, and dysmorphic facial features. Some patients may have seizures or abnormalities on brain imaging. All reported patients have died in infancy.\r\n\r\n4 individuals from 3 unrelated families with typical features of Galloway-Mowat syndrome including proteinuria, microcephaly, developmental delay and brain malformations. Supportive functional data. \nSources: Expert list",
"entity_name": "YRDC",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:19:16.696618+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4292",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: ZNF526 as Green List (high evidence)",
"entity_name": "ZNF526",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:19:16.679066+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4292",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: znf526 has been classified as Green List (High Evidence).",
"entity_name": "ZNF526",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:19:06.550852+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4291",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: ZNF526 was added\ngene: ZNF526 was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: ZNF526 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ZNF526 were set to PMID: 33397746, 21937992, 25558065,\nPhenotypes for gene: ZNF526 were set to Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia\nReview for gene: ZNF526 was set to GREEN\nAdded comment: - PMID: 21937992 (2011) - Two unrelated families (with 4 affected individuals in each) with non-syndromic ID (mild or moderate, respectively) identified harbouring different biallelic missense variants in the ZNF526 gene.\r\n\r\n- PMID: 25558065 (2015) - One family with ID, Noonan-like facies, pulmonary stenosis and a homozygous missense variant in this gene. No further details provided.\r\n\r\n- PMID: 33397746 (2021) - Five individuals from four unrelated families with homozygous ZNF526 variants. Four harboured truncating variants, and were all affected by profound DD and severe ID, severe pre/postnatal microcephaly (ranging from -4 SD to -8 SD), bilateral progressive cataracts, hypertonic-dystonic movements, epilepsy and brain MRI anomalies. The fifth patient had a homozygous missense variant and a slightly less severe disorder, with postnatal microcephaly (-2 SD), progressive bilateral cataracts, severe ID, and normal brain MRI. Zebrafish model demonstrated brain and eye malformations resembling findings seen in the human holoprosencephaly spectrum \nSources: Expert list",
"entity_name": "ZNF526",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:18:23.089325+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4290",
"user_name": "Daniel Flanagan",
"item_type": "entity",
"text": "gene: PIDD1 was added\ngene: PIDD1 was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PIDD1 were set to 28397838; 29302074; 33414379; 34163010\nPhenotypes for gene: PIDD1 were set to Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum\nReview for gene: PIDD1 was set to AMBER\nAdded comment: Doesn't appear to have an antenatal onset. Clinical findings in supplementary table for PMID: 34163010 doesn't mention any prenatal findings. For family M278, two affected siblings were \"born at term after uneventful pregnancies, neonatal periods and normal development.\" Mean age of cohort was 13.2 years. \r\n\r\nBiallelic PIDD1 pathogenic variants have been reported in 26 individuals (11 families) with DD (all), variable degrees of ID (mild to severe), behavioral (eg. aggression/self-mutilation in several, ADHD) and/or psychiatric abnormalities (ASD, psychosis in 5 belonging to 3 families), well-controlled epilepsy is some (9 subjects from 6 families) and MRI abnormalities notably abnormal gyration pattern (pachygyria with predominant anterior gradient) as well as corpus callosum anomalies (commonly thinning) in several. Dysmorphic features have been reported in almost all, although there has been no specific feature suggested.\r\n\r\nThe first reports on the phenotype associated with biallelic PIDD1 mutations were made by Harripaul et al (2018 - PMID: 28397838) and Hu et al (2019 - PMID: 29302074) [both studies investigating large cohorts of individuals with ID from consanguineous families].\r\n\r\nSheikh et al (2021 - PMID: 33414379) provided details on the phenotype of 15 individuals from 5 families including those from the previous 2 reports and studied provided evidence on the role of PIDD1 and the effect of variants.\r\n\r\nZaki et al (2021 - PMID: 34163010) reported 11 additional individuals from 6 consanguineous families, summarize the features of all subjects published in the literature and review the neuroradiological features of the disorder.\r\n\r\nPIDD1 encodes p53-induced death domain protein 1. The protein is part of the PIDDosome, a multiprotein complex also composed of the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 and induces apoptosis in response to DNA damage.\r\n\r\nThere are 5 potential PIDD1 mRNA transcript variants with NM_145886.4 corresponding to the longest. Similar to the protein encoded by CRADD, PIDD1 contains a death domain (DD - aa 774-893). Constitutive post-translational processing gives PIDD1-N, PIDD1-C the latter further processed into PIDD1-CC (by auto-cleavage). Serine residues at pos. 446 and 588 are involved in this autoprocessing generating PIDD1-C (aa 446-910) and PIDD1-CC (aa 774-893). The latter is needed for caspase-2 activation.\r\n\r\nMost (if not all) individuals belonged to consanguineous families of different origins and harbored pLoF or missense variants.\r\n\r\nVariants reported so far include : c.2587C>T; p.Gln863* / c.1909C>T ; p.Arg637* / c.2443C>T / p.Arg815Trp / c.2275-1G>A which upon trap assay was shown to lead to skipping of ex15 with direct splicing form exon14 to the terminal exon 16 (resulting to p.Arg759Glyfs*1 with exlcusion of the entire DD) / c.2584C>T; p.Arg862Trp / c.1340G>A; p.Trp447* / c.2116_2120del; p.Val706His*, c.1564_1565del; p.Gly602fs*26\r\n\r\nEvidence so far provided includes:\r\n- Biallelic CRADD variants cause a NDD disorder and a highly similar gyration pattern.\r\n- Confirmation of splicing effect (eg. for c.2275-1G>A premature stop in position 760) or poor expression (NM_145886.3:c.2587C>T; p.Gln863*). Arg815Trp did not affect autoprocessing or protein stability.\r\n- Abnormal localization pattern, loss of interaction with CRADD and failure to activate caspase-2 (MDM2 cleavage assay) [p.Gln863* and Arg815Trp]\r\n- Available expression data from GTEx (PIDD1 having broad expression in multiple tissues, but higher in brain cerebellum) as well as BrainSpan and PsychEncode studies suggesting high coexpression of PIDD1, CRADD and CASP2 in many regions in the developing human brain.\r\n- Variants in other genes encoding proteins interacting with PIDD1 (MADD, FADD, DNAJ, etc) are associated with NDD.\r\n\r\nPidd-1 ko mice (ex3-15 removal) lack however CNS-related phenotypes. These show decreased anxiety but no motor anomalies. This has also been the case with Cradd-/- mice displaying no significant CNS phenotypes without lamination defects. \nSources: Expert list",
"entity_name": "PIDD1",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:16:01.675714+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4290",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: ZNF668 as Amber List (moderate evidence)",
"entity_name": "ZNF668",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:16:01.665598+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4290",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: znf668 has been classified as Amber List (Moderate Evidence).",
"entity_name": "ZNF668",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:15:51.761698+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4289",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: ZNF668 was added\ngene: ZNF668 was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: ZNF668 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ZNF668 were set to PMID: 34313816, 26633546\nPhenotypes for gene: ZNF668 were set to DNA damage repair defect; microcephaly; growth deficiency; severe global developmental delay; brain malformation; facial dysmorphism\nReview for gene: ZNF668 was set to AMBER\nAdded comment: 2 consanguineous families reported with different biallelic truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism. Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts. \nSources: Expert list",
"entity_name": "ZNF668",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:13:23.977486+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4288",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: ZNHIT3 as Green List (high evidence)",
"entity_name": "ZNHIT3",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:13:23.966666+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4288",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: znhit3 has been classified as Green List (High Evidence).",
"entity_name": "ZNHIT3",
"entity_type": "gene"
},
{
"created": "2022-02-28T17:13:14.388515+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "0.4287",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: ZNHIT3 was added\ngene: ZNHIT3 was added to Fetal anomalies. Sources: Expert list\nMode of inheritance for gene: ZNHIT3 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ZNHIT3 were set to PMID: 28335020; 28335020; 31048081\nPhenotypes for gene: ZNHIT3 were set to PEHO syndrome, MIM# 260565\nReview for gene: ZNHIT3 was set to GREEN\nAdded comment: PEHO is a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy due to almost total loss of granule neurons. Affected individuals present in early infancy with hypotonia, profoundly delayed psychomotor development, optic atrophy, progressive atrophy of the cerebellum and brainstem, and dysmyelination. Most patients also develop infantile seizures that are often associated with hypsarrhythmia on EEG, and many have peripheral oedema. More than 20 affected individuals reported of Finnish origin, p.Ser31Leu is a founder variant. One compound het reported and supportive animal model. \nSources: Expert list",
"entity_name": "ZNHIT3",
"entity_type": "gene"
}
]
}