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{
"count": 220751,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1582",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1580",
"results": [
{
"created": "2020-09-19T11:07:09.599082+10:00",
"panel_name": "Cardiomyopathy_Paediatric",
"panel_id": 3270,
"panel_version": "0.11",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fnip1 has been classified as Green List (High Evidence).",
"entity_name": "FNIP1",
"entity_type": "gene"
},
{
"created": "2020-09-19T11:06:58.588235+10:00",
"panel_name": "Cardiomyopathy_Paediatric",
"panel_id": 3270,
"panel_version": "0.10",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: FNIP1 was added\ngene: FNIP1 was added to Cardiomyopathy_Paediatric. Sources: Literature\nMode of inheritance for gene: FNIP1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: FNIP1 were set to 32181500; 32905580\nPhenotypes for gene: FNIP1 were set to Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia\nReview for gene: FNIP1 was set to GREEN\nAdded comment: - PMID: 32181500 (2020) - Three patients from two independent consanguineous families with homozygous variants (c.3353G>A, p.Ser1118Asn and c.1289delA, p.His430Profs7*) in the FNIP1 gene. Both variants segregated with the disease phenotype in each family. Clinically, patients presented with combined immunodeficiency, cardiac findings (hypertrophic cardiomyopathy, Wolff‐Parkinson‐White syndrome), and myopathy of skeletal muscles with motor DD. Authors note phenotypic overlap with the murine model of FNIP1 deficiency, but no functional analyses of the variants or patient cells were performed.\r\n\r\n- PMID: 32905580 (2020) - Three cases from unrelated families, all harbouring novel biallelic variants in FNIP1. Clinical manifestations in all patients include hypertrophic cardiomyopathy, severe and/or recurrent infections, absent circulating B-cells, and agammaglobulinemia; as well as either severe or intermittent neutropenia in two cases. Functional studies showed impairment of B-cell metabolism, including disruptions to mitochondrial numbers/activity and the PI3K/AKT pathway. \nSources: Literature",
"entity_name": "FNIP1",
"entity_type": "gene"
},
{
"created": "2020-09-19T11:06:36.716060+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4499",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: FNIP1 as ready",
"entity_name": "FNIP1",
"entity_type": "gene"
},
{
"created": "2020-09-19T11:06:36.706003+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4499",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fnip1 has been classified as Green List (High Evidence).",
"entity_name": "FNIP1",
"entity_type": "gene"
},
{
"created": "2020-09-19T11:05:32.548619+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4499",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: FNIP1 as Green List (high evidence)",
"entity_name": "FNIP1",
"entity_type": "gene"
},
{
"created": "2020-09-19T11:05:32.539174+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4499",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: fnip1 has been classified as Green List (High Evidence).",
"entity_name": "FNIP1",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:46:11.605957+10:00",
"panel_name": "Hereditary Neuropathy - complex",
"panel_id": 3070,
"panel_version": "0.79",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: NEMF as ready",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:46:11.595266+10:00",
"panel_name": "Hereditary Neuropathy - complex",
"panel_id": 3070,
"panel_version": "0.79",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: nemf has been classified as Green List (High Evidence).",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:46:06.290411+10:00",
"panel_name": "Hereditary Neuropathy - complex",
"panel_id": 3070,
"panel_version": "0.79",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: NEMF as Green List (high evidence)",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:46:06.282299+10:00",
"panel_name": "Hereditary Neuropathy - complex",
"panel_id": 3070,
"panel_version": "0.79",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: nemf has been classified as Green List (High Evidence).",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:45:57.714937+10:00",
"panel_name": "Hereditary Neuropathy - complex",
"panel_id": 3070,
"panel_version": "0.78",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: NEMF was added\ngene: NEMF was added to Hereditary Neuropathy - complex. Sources: Literature\nMode of inheritance for gene: NEMF was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: NEMF were set to 32934225\nPhenotypes for gene: NEMF were set to Intellectual disability; neuropathy\nReview for gene: NEMF was set to GREEN\nAdded comment: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration. \nSources: Literature",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:44:51.146857+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3013",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: NEMF as ready",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:44:51.138387+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3013",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: nemf has been classified as Green List (High Evidence).",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:44:45.537916+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3013",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: NEMF as Green List (high evidence)",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:44:45.528065+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3013",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: nemf has been classified as Green List (High Evidence).",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:44:16.315628+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3012",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: NEMF was added\ngene: NEMF was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: NEMF was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: NEMF were set to 32934225\nPhenotypes for gene: NEMF were set to Intellectual disability; neuropathy\nReview for gene: NEMF was set to GREEN\nAdded comment: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration. \nSources: Literature",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:43:23.170505+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4498",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: NEMF as ready",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:43:23.152263+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4498",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: nemf has been classified as Green List (High Evidence).",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:43:15.265780+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4498",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: NEMF as Green List (high evidence)",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:43:15.256666+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4498",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: nemf has been classified as Green List (High Evidence).",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T08:42:25.636660+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4497",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: NEMF was added\ngene: NEMF was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: NEMF was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: NEMF were set to 32934225\nPhenotypes for gene: NEMF were set to Intellectual disability; neuropathy\nReview for gene: NEMF was set to GREEN\nAdded comment: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration. \nSources: Literature",
"entity_name": "NEMF",
"entity_type": "gene"
},
{
"created": "2020-09-19T00:13:06.792395+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4496",
"user_name": "Arina Puzriakova",
"item_type": "entity",
"text": "gene: FNIP1 was added\ngene: FNIP1 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: FNIP1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: FNIP1 were set to 32181500; 32905580\nPhenotypes for gene: FNIP1 were set to Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia\nReview for gene: FNIP1 was set to GREEN\nAdded comment: - PMID: 32181500 (2020) - Three patients from two independent consanguineous families with homozygous variants (c.3353G>A, p.Ser1118Asn and c.1289delA, p.His430Profs7*) in the FNIP1 gene. Both variants segregated with the disease phenotype in each family. Clinically, patients presented with combined immunodeficiency, cardiac findings (hypertrophic cardiomyopathy, Wolff‐Parkinson‐White syndrome), and myopathy of skeletal muscles with motor DD. Authors note phenotypic overlap with the murine model of FNIP1 deficiency, but no functional analyses of the variants or patient cells were performed.\r\n\r\n- PMID: 32905580 (2020) - Three cases from unrelated families, all harbouring novel biallelic variants in FNIP1. Clinical manifestations in all patients include hypertrophic cardiomyopathy, severe and/or recurrent infections, absent circulating B-cells, and agammaglobulinemia; as well as either severe or intermittent neutropenia in two cases. Functional studies showed impairment of B-cell metabolism, including disruptions to mitochondrial numbers/activity and the PI3K/AKT pathway. \nSources: Literature",
"entity_name": "FNIP1",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:43:58.897426+10:00",
"panel_name": "Mackenzie's Mission_Reproductive Carrier Screening",
"panel_id": 3139,
"panel_version": "0.23",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: DSTYK: Rating: AMBER; Mode of pathogenicity: None; Publications: 28157540, 23862974; Phenotypes: Spastic paraplegia 23, MIM# 270750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:42:21.069277+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Tag SV/CNV tag was added to gene: DSTYK.\nTag founder tag was added to gene: DSTYK.",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:42:10.467851+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: DSTYK as ready",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:42:10.456936+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dstyk has been classified as Amber List (Moderate Evidence).",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:42:07.810295+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: DSTYK were changed from Congenital anomalies of kidney and urinary tract 1, 610805, AD; Spastic paraplegia 23, 270750; Spastic paraplegia 23, 270750, AR to Spastic paraplegia 23, MIM#270750",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:41:40.828919+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.123",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: DSTYK were set to ",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:41:28.723831+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.122",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: DSTYK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:41:17.928866+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.121",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: DSTYK as Amber List (moderate evidence)",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:41:17.918230+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.121",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dstyk has been classified as Amber List (Moderate Evidence).",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T17:41:04.051484+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.120",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: DSTYK: Rating: AMBER; Mode of pathogenicity: None; Publications: 28157540, 23862974; Phenotypes: Spastic paraplegia 23, MIM# 270750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DSTYK",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:58:06.677965+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4496",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: TAOK1 as ready",
"entity_name": "TAOK1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:58:06.660798+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4496",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: taok1 has been classified as Green List (High Evidence).",
"entity_name": "TAOK1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:57:59.530667+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4496",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: TAOK1 were changed from to TAOK1-related neurodevelopmental disorder",
"entity_name": "TAOK1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:57:40.770784+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4495",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: TAOK1 were set to ",
"entity_name": "TAOK1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:57:24.913581+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4494",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: TAOK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "TAOK1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:57:07.284666+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4493",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "changed review comment from: Monoallelic de novo variants reported in 8 individuals with nonspecific phenotype of intellectual disability and hypotonia. Most were LOF, 2 missense. 3 had macrocephaly.; to: Monoallelic de novo variants reported in 8 individuals with nonspecific phenotype of intellectual disability and hypotonia; 3 had macrocephaly.",
"entity_name": "TAOK1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:56:32.036976+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4493",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: TAOK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31230721; Phenotypes: TAOK1-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "TAOK1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:52:09.846943+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4493",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CSF1R as ready",
"entity_name": "CSF1R",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:52:09.827659+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4493",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: csf1r has been classified as Green List (High Evidence).",
"entity_name": "CSF1R",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:52:02.261565+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4493",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CSF1R were changed from to Brain abnormalities, neurodegeneration, and dysosteosclerosis, (MIM#618476); Leukoencephalopathy, diffuse hereditary, with spheroids, (MIM#221820)",
"entity_name": "CSF1R",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:51:42.655906+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4492",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: CSF1R were set to ",
"entity_name": "CSF1R",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:51:16.914838+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4491",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of pathogenicity for gene: CSF1R was changed from to Other",
"entity_name": "CSF1R",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:50:58.901432+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4490",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: CSF1R was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal",
"entity_name": "CSF1R",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:37:15.587105+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4489",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "reviewed gene: TAOK1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31230721; Phenotypes: Neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown",
"entity_name": "TAOK1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:34:43.122710+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4489",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: L2HGDH as ready",
"entity_name": "L2HGDH",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:34:43.111801+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4489",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: l2hgdh has been classified as Green List (High Evidence).",
"entity_name": "L2HGDH",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:34:36.934469+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4489",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: L2HGDH were changed from to L-2-hydroxyglutaric aciduria, MIM#236792",
"entity_name": "L2HGDH",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:34:12.588187+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4488",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: L2HGDH were set to ",
"entity_name": "L2HGDH",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:33:46.600276+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4487",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: L2HGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "L2HGDH",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:33:27.715311+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4486",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: L2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 15385440; Phenotypes: L-2-hydroxyglutaric aciduria, MIM#236792; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "L2HGDH",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:33:00.488691+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4486",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31330095, 24336230; Phenotypes: Brain abnormalities, neurodegeneration, and dysosteosclerosis, (MIM#618476), Leukoencephalopathy, diffuse hereditary, with spheroids, (MIM#221820); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal",
"entity_name": "CSF1R",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:29:07.775435+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4486",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: LMNB1 as ready",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:29:07.764585+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4486",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: lmnb1 has been classified as Green List (High Evidence).",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:29:00.113360+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4486",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: LMNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:28:42.201908+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4485",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of pathogenicity for gene: LMNB1 was changed from to Other",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:28:26.352792+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4484",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: LMNB1 were set to ",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:28:03.578194+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4483",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: LMNB1 were changed from to Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis; Leukodystrophy, adult-onset, autosomal dominant, MIM#169500",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:27:39.764844+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4482",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Tag SV/CNV tag was added to gene: LMNB1.",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:27:25.590958+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4482",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: LMNB1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32910914, 16951681, 19151023; Phenotypes: Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis, Leukodystrophy, adult-onset, autosomal dominant, MIM#169500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:23:51.113627+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.483",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: LMNB1 as ready",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:23:51.098378+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.483",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: lmnb1 has been classified as Green List (High Evidence).",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:23:46.536281+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.483",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: LMNB1 as Green List (high evidence)",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:23:46.518524+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.483",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: lmnb1 has been classified as Green List (High Evidence).",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:23:17.559922+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.482",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: LMNB1 was added\ngene: LMNB1 was added to Microcephaly. Sources: Literature\nMode of inheritance for gene: LMNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: LMNB1 were set to 32910914\nPhenotypes for gene: LMNB1 were set to Global developmental delay; Intellectual disability; Microcephaly; Short stature; Seizures; Abnormality of the corpus callosum; Cortical gyral simplification; Feeding difficulties; Scoliosis\nMode of pathogenicity for gene: LMNB1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: LMNB1 was set to GREEN\nAdded comment: Cristofoli et al (2020 - PMID: 32910914) report 7 individuals (from 5 families) harboring mostly de novo LMNB1 variants. The common phenotype consisted of primary microcephaly (7/7 ranging from -4.4 to -10 SD), DD/ID (7/7), relative short stature in most (+0.7 to -4 SD). Additional features included brain MRI abnormalities (abnormal CC in 3, simplified gyral pattern in 3, small structurally normal brain, etc), seizures (4 individuals from 2 families), limb spasticity (1/7), cortical visual impairment (in 3), feeding difficulties (5/7), scoliosis (4/7). Non-overlapping dysmorphic features were reported in some. Variants were identified by WES or custom-designed gene panel and included 3 missense variants, 1 in-frame deletion and a splice variant. The in-frame deletion was inherited from a similarly affected parent in whom the variant occurred as a dn event. The splice SNV(NM_005573.3:c.939+1G>A) occurred in 3 sibs and was present as mosaic variant (15%) in the parent. This variant was predicted to result to extension of exon 5 by 6 amino-acids (samples were unavailable for mRNA studies). LMNB1 encodes a B-type lamin (the other being encoded by LMNB2). A- and B- type lamins are major components of the nuclear lamina. As the authors comment, LMNB1 is expressed in almost all cell types beginning at the earliest stages of development. Lamin-deficient mouse models support an essential role of B-type lamins in organogenesis, neuronal migration, patterning during brain development. Functional studies performed, demonstrated impaired formation of LMNB1 nuclear lamina in LMNB1-null HeLa cells transfected with cDNAs for 3 missense variants. Two variants (Lys33Glu/Arg42Trp) were shown to result in decreased nuclear localization with increased abundance in the cytosolic fraction. In patient derived LCLs these variants led to abnormal nuclear morphology. A missense variant in another domain (Ala152Gly - 1st coil domain) resulted also in lower abundance of lamin B1, irregular lamin A/C nuclear lamina, as well as more condensed nuclei (HeLa cells). LMNB1 duplications or missense mutations increasing LMNB1 expression are associated with a different presentation of AD leuodystrophy. A variant previously associated with leukodystrophy (Arg29Trp) was shown to behave differently (present in the nuclear extract but not in the cytosol, lamin B1 to A/C ratio in nuclear extract was not significantly altered compared to wt as was the case for Arg42Trp, Lys33Glu). Given the pLI score of 0.55 as well as the phenotype of individuals with deletions (not presenting microcephaly) the authors predict that a dominant-negative effect applies (rather than haploinsufficiency). \nSources: Literature",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:21:10.616153+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4482",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "reviewed gene: L2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20052767; Phenotypes: L-2-hydroxyglutaric aciduria MIM#236792; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "L2HGDH",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:18:27.245940+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.862",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: LMNB1 as ready",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:18:27.239309+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.862",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: Note different mechanism for LMNB1-related neurodevelopmental phenotype cf Adult-onset leukodystrophy phenotype previously associated with this gene.",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:18:27.172762+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.862",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: lmnb1 has been classified as Amber List (Moderate Evidence).",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:18:07.021777+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.862",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of pathogenicity for gene: LMNB1 was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:17:11.043820+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.861",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: LMNB1 as Amber List (moderate evidence)",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:17:11.034253+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.861",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: lmnb1 has been classified as Amber List (Moderate Evidence).",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:15:30.303136+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3011",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: LMNB1 as ready",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:15:30.298785+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3011",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: Note different mechanism for LMNB1-related neurodevelopmental phenotype cf Adult-onset leukodystrophy phenotype previously associated with this gene.",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:15:30.276274+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3011",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: lmnb1 has been classified as Green List (High Evidence).",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:14:43.643347+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3011",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: LMNB1 were changed from Leukodystrophy, adult-onset, autosomal dominant, MIM#169500 to Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis; Leukodystrophy, adult-onset, autosomal dominant, MIM#169500",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:13:32.118661+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3010",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: LMNB1 were set to ",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:12:55.545828+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3009",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of pathogenicity for gene: LMNB1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:12:25.275953+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3008",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: LMNB1 as Green List (high evidence)",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:12:25.264870+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3008",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: lmnb1 has been classified as Green List (High Evidence).",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:10:14.400748+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.162",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MAPK8 as ready",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:10:14.391323+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.162",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mapk8 has been classified as Amber List (Moderate Evidence).",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:10:10.554968+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.162",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: MAPK8 as Amber List (moderate evidence)",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:10:10.537577+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.162",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mapk8 has been classified as Amber List (Moderate Evidence).",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:09:42.273368+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.161",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: MAPK8 was added\ngene: MAPK8 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: MAPK8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: MAPK8 were set to 31784499\nPhenotypes for gene: MAPK8 were set to Chronic mucocutaneous candidiasis; Connective tissue disorders\nReview for gene: MAPK8 was set to AMBER\nAdded comment: PMID: 31784499 (2020) - Three cases in a single family with chronic mucocutaneous candidiasis and a connective tissue disorder that clinically overlaps with hEDS. WES revealed a splice-site variant (c.311+1G>A) in the MAPK8 gene that segregated with the disorder. Includes supportive functional data using patient-derived fibroblasts, showing that the variant impairs IL-17A/F immunity and the development of Th17 cells. \r\n\r\nSingle family with high level of supportive functional data. \nSources: Literature",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T11:00:01.812192+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4482",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: MAPK8: Rating: AMBER; Mode of pathogenicity: None; Publications: 31784499; Phenotypes: Chronic mucocutaneous candidiasis, Connective tissue disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:58:48.283809+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4482",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MAPK8 as ready",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:58:48.266079+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4482",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mapk8 has been classified as Amber List (Moderate Evidence).",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:58:16.831434+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4482",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: MAPK8 as Amber List (moderate evidence)",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:58:16.813667+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4482",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mapk8 has been classified as Amber List (Moderate Evidence).",
"entity_name": "MAPK8",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:52:34.347102+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4481",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CTNNBL1 as ready",
"entity_name": "CTNNBL1",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:52:34.329704+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4481",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ctnnbl1 has been classified as Amber List (Moderate Evidence).",
"entity_name": "CTNNBL1",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:52:24.101117+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4481",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CTNNBL1 as Amber List (moderate evidence)",
"entity_name": "CTNNBL1",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:52:24.091614+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4481",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ctnnbl1 has been classified as Amber List (Moderate Evidence).",
"entity_name": "CTNNBL1",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:03:52.569414+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.860",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "edited their review of gene: LMNB1: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:03:37.284232+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3007",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "edited their review of gene: LMNB1: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:03:06.235831+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.860",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: LMNB1 was added\ngene: LMNB1 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: LMNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: LMNB1 were set to 32910914\nPhenotypes for gene: LMNB1 were set to Global developmental delay; Intellectual disability; Microcephaly; Short stature; Seizures; Abnormality of the corpus callosum; Cortical gyral simplification; Feeding difficulties; Scoliosis\nPenetrance for gene: LMNB1 were set to unknown\nMode of pathogenicity for gene: LMNB1 was set to Other\nReview for gene: LMNB1 was set to AMBER\nAdded comment: Cristofoli et al (2020 - PMID: 32910914) report 7 individuals (from 5 families) harboring mostly de novo LMNB1 variants. \r\n\r\nThe common phenotype consisted of primary microcephaly (7/7 ranging from -4.4 to -10 SD), DD/ID (7/7), relative short stature in most (+0.7 to -4 SD). Additional features included brain MRI abnormalities (abnormal CC in 3, simplified gyral pattern in 3, small structurally normal brain, etc), seizures (4 individuals from 2 families), limb spasticity (1/7), cortical visual impairment (in 3), feeding difficulties (5/7), scoliosis (4/7). Non-overlapping dysmorphic features were reported in some.\r\n\r\nVariants were identified by WES or custom-designed gene panel and included 3 missense variants, 1 in-frame deletion and a splice variant. The in-frame deletion was inherited from a similarly affected parent in whom the variant occurred as a dn event. The splice SNV(NM_005573.3:c.939+1G>A) occurred in 3 sibs and was present as mosaic variant (15%) in the parent. This variant was predicted to result to extension of exon 5 by 6 amino-acids (samples were unavailable for mRNA studies).\r\n\r\nLMNB1 encodes a B-type lamin (the other being encoded by LMNB2). A- and B- type lamins are major components of the nuclear lamina. As the authors comment, LMNB1 is expressed in almost all cell types beginning at the earliest stages of development.\r\n\r\nLamin-deficient mouse models support an essential role of B-type lamins in organogenesis, neuronal migration, patterning during brain development.\r\n\r\nFunctional studies performed, demonstrated impaired formation of LMNB1 nuclear lamina in LMNB1-null HeLa cells transfected with cDNAs for 3 missense variants. \r\n\r\nTwo variants (Lys33Glu/Arg42Trp) were shown to result in decreased nuclear localization with increased abundance in the cytosolic fraction. In patient derived LCLs these variants led to abnormal nuclear morphology. A missense variant in another domain (Ala152Gly - 1st coil domain) resulted also in lower abundance of lamin B1, irregular lamin A/C nuclear lamina, as well as more condensed nuclei (HeLa cells).\r\n\r\nLMNB1 duplications or missense mutations increasing LMNB1 expression are associated with a different presentation of AD leuodystrophy. A variant previously associated with leukodystrophy (Arg29Trp) was shown to behave differently (present in the nuclear extract but not in the cytosol, lamin B1 to A/C ratio in nuclear extract was not significantly altered compared to wt as was the case for Arg42Trp, Lys33Glu).\r\n\r\nGiven the pLI score of 0.55 as well as the phenotype of individuals with deletions (not presenting microcephaly) the authors predict that a dominant-negative effect applies (rather than haploinsufficiency).\r\n\r\nConsider inclusion in the following panels : DD/ID (green), epilepsy (amber - 4 of 7 patients belonging to 2 families), primary microcephaly (green), callosome (amber/green - 3 individuals belonging to 3 families), mendeliome (green), etc. \nSources: Literature",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:02:53.018898+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3007",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "edited their review of gene: LMNB1: Changed mode of pathogenicity: Other",
"entity_name": "LMNB1",
"entity_type": "gene"
},
{
"created": "2020-09-18T10:01:59.563336+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3007",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "reviewed gene: LMNB1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 32910914; Phenotypes: Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown",
"entity_name": "LMNB1",
"entity_type": "gene"
}
]
}