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{
"count": 220497,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1544",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1542",
"results": [
{
"created": "2020-10-11T14:43:30.221245+11:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.49",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: GZF1 as Green List (high evidence)",
"entity_name": "GZF1",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:43:30.212914+11:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.49",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: gzf1 has been classified as Green List (High Evidence).",
"entity_name": "GZF1",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:43:00.541328+11:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.48",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817, 28475863; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GZF1",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:41:33.536378+11:00",
"panel_name": "Stickler Syndrome",
"panel_id": 3114,
"panel_version": "0.6",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: GZF1 as ready",
"entity_name": "GZF1",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:41:33.529177+11:00",
"panel_name": "Stickler Syndrome",
"panel_id": 3114,
"panel_version": "0.6",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: gzf1 has been classified as Green List (High Evidence).",
"entity_name": "GZF1",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:41:31.112901+11:00",
"panel_name": "Stickler Syndrome",
"panel_id": 3114,
"panel_version": "0.6",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GZF1 were changed from to Joint laxity, short stature, and myopia, MIM# 617662",
"entity_name": "GZF1",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:41:22.715502+11:00",
"panel_name": "Stickler Syndrome",
"panel_id": 3114,
"panel_version": "0.5",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GZF1 were set to ",
"entity_name": "GZF1",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:41:14.417270+11:00",
"panel_name": "Stickler Syndrome",
"panel_id": 3114,
"panel_version": "0.4",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: GZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GZF1",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:41:05.105710+11:00",
"panel_name": "Stickler Syndrome",
"panel_id": 3114,
"panel_version": "0.3",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817, 28475863; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GZF1",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:35:48.397441+11:00",
"panel_name": "Syndromic Retinopathy",
"panel_id": 3099,
"panel_version": "0.104",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "changed review comment from: Bi-allelic variants cause CLN, retinal degeneration prominent. However, also reports of retinal abnormalities with mono-allelic variants, which are typically associated with a frontotemporal dementia phenotype.; to: Bi-allelic variants cause CLN, retinal degeneration prominent. However, also limited reports of retinal abnormalities with mono-allelic variants, which are typically associated with a frontotemporal dementia phenotype.",
"entity_name": "GRN",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:35:32.996008+11:00",
"panel_name": "Syndromic Retinopathy",
"panel_id": 3099,
"panel_version": "0.104",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GRN were set to ",
"entity_name": "GRN",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:35:15.128728+11:00",
"panel_name": "Syndromic Retinopathy",
"panel_id": 3099,
"panel_version": "0.103",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: GRN: Added comment: Bi-allelic variants cause CLN, retinal degeneration prominent. However, also reports of retinal abnormalities with mono-allelic variants, which are typically associated with a frontotemporal dementia phenotype.; Changed publications: 31855245, 28404863, 30922528",
"entity_name": "GRN",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:15:30.124985+11:00",
"panel_name": "Congenital Stationary Night Blindness",
"panel_id": 283,
"panel_version": "0.6",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: GNB3 were changed from Night blindness, congenital stationary, type 1h to Night blindness, congenital stationary, type 1H, MIM# 617024",
"entity_name": "GNB3",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:14:05.123415+11:00",
"panel_name": "Congenital Stationary Night Blindness",
"panel_id": 283,
"panel_version": "0.5",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: GNB3 as ready",
"entity_name": "GNB3",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:14:05.115909+11:00",
"panel_name": "Congenital Stationary Night Blindness",
"panel_id": 283,
"panel_version": "0.5",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: gnb3 has been classified as Green List (High Evidence).",
"entity_name": "GNB3",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:14:02.454889+11:00",
"panel_name": "Congenital Stationary Night Blindness",
"panel_id": 283,
"panel_version": "0.5",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: GNB3 were set to ",
"entity_name": "GNB3",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:13:50.756451+11:00",
"panel_name": "Congenital Stationary Night Blindness",
"panel_id": 283,
"panel_version": "0.4",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: GNB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27063057, 17065478; Phenotypes: Night blindness, congenital stationary, type 1H, MIM# 617024; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "GNB3",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:05:15.784986+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4875",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: ITFG2 as ready",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:05:15.777059+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4875",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: itfg2 has been classified as Amber List (Moderate Evidence).",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:05:07.877368+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4875",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: ITFG2 as Amber List (moderate evidence)",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:05:07.866728+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4875",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: itfg2 has been classified as Amber List (Moderate Evidence).",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:04:50.554259+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4874",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: ITFG2 was added\ngene: ITFG2 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: ITFG2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z\nPhenotypes for gene: ITFG2 were set to Neurodevelopmental abnormality; Intellectual disability; Developmental regression; Ataxia\nReview for gene: ITFG2 was set to AMBER\nAdded comment: ITFG2 was suggested to be a candidate gene for autosomal recessive ID in the study by Harripaul et al (2018 - PMID: 28397838). The authors performed microarray and exome sequencing in 192 consanguineous families and identified a homozygous ITGF2 stopgain variant (NM_018463.3:c.472G>T / p.Glu158*) along with 3 additional variants segregating with ID within an investigated family (PK51). Cheema et al (2020 - https://doi.org/10.1038/s41525-020-00150-z) report briefly on a male, born to consanguineous parents presenting with NDD, seizures, regression and ataxia. There was a similarly affected female sibling. Evaluation of ROH revealed a homozygous ITFG2 nonsense variant [NM_018463.3:c.361C>T / p.(Gln121*)]. Families in this study were investigated by trio WES or WGS. Evaluation of data of the same lab revealed 3 additional unrelated subjects with overlapping phenotypes, notably NDD and ataxia. These individuals were - each - homozygous for pLoF variants [NM_018463.3:c.848-1G>A; NM_018463.3:c.704dupC, p.(Ala236fs), NM_018463.3:c.1000_1001delAT, p.(Ile334fs)]. As discussed in OMIM, ITFG2 encodes a subunit of the KICSTOR protein complex, having a role in regulating nutrient sensing by MTOR complex-1 (Wolfson et al 2017 - PMID : 28199306).\r\n\r\nRated Amber as Cheema et al report on diagnostic outcomes and multiple candidate genes as part of a heterogenous cohort and details are therefore limited. \nSources: Literature",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:01:40.018612+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3064",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: ITFG2 as ready",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:01:39.999358+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3064",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: Agree with Amber rating, considering reported as part of heterogenous cohort reporting diagnostic outcomes and multiple candidate genes.",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:01:39.965151+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3064",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: itfg2 has been classified as Amber List (Moderate Evidence).",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:01:01.011291+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3064",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: ITFG2 as Amber List (moderate evidence)",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T14:01:01.003733+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3064",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: itfg2 has been classified as Amber List (Moderate Evidence).",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:28:18.772517+11:00",
"panel_name": "Polymicrogyria and Schizencephaly",
"panel_id": 18,
"panel_version": "0.155",
"user_name": "Zornitza Stark",
"item_type": "panel",
"text": "Panel types changed to Australian Genomics; Victorian Clinical Genetics Services; Rare Disease",
"entity_name": null,
"entity_type": null
},
{
"created": "2020-10-11T13:26:00.870835+11:00",
"panel_name": "Callosome",
"panel_id": 205,
"panel_version": "0.220",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SHMT2 as ready",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:26:00.860649+11:00",
"panel_name": "Callosome",
"panel_id": 205,
"panel_version": "0.220",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:25:54.674189+11:00",
"panel_name": "Polymicrogyria and Schizencephaly",
"panel_id": 18,
"panel_version": "0.154",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SHMT2 as ready",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:25:54.660934+11:00",
"panel_name": "Polymicrogyria and Schizencephaly",
"panel_id": 18,
"panel_version": "0.154",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:25:49.017905+11:00",
"panel_name": "Polymicrogyria and Schizencephaly",
"panel_id": 18,
"panel_version": "0.154",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SHMT2 as Green List (high evidence)",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:25:49.010085+11:00",
"panel_name": "Polymicrogyria and Schizencephaly",
"panel_id": 18,
"panel_version": "0.154",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:25:20.889097+11:00",
"panel_name": "Polymicrogyria and Schizencephaly",
"panel_id": 18,
"panel_version": "0.153",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: SHMT2 was added\ngene: SHMT2 was added to Polymicrogyria and Schizencephaly. Sources: Literature\nMode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SHMT2 were set to 33015733\nPhenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly\nReview for gene: SHMT2 was set to GREEN\nAdded comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.\r\n\r\nAll affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.\r\n\r\nBiallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. \r\n\r\nSHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.\r\n\r\nMitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.\r\n\r\nWhile plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.\r\n\r\nShmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.\r\n\r\nThe authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). \nSources: Literature",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:25:17.707974+11:00",
"panel_name": "Callosome",
"panel_id": 205,
"panel_version": "0.220",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SHMT2 as Green List (high evidence)",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:25:17.699887+11:00",
"panel_name": "Callosome",
"panel_id": 205,
"panel_version": "0.220",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:24:48.995267+11:00",
"panel_name": "Callosome",
"panel_id": 205,
"panel_version": "0.219",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: SHMT2 was added\ngene: SHMT2 was added to Callosome. Sources: Literature\nMode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SHMT2 were set to 33015733\nPhenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly\nReview for gene: SHMT2 was set to GREEN\nAdded comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.\r\n\r\nAll affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.\r\n\r\nBiallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. \r\n\r\nSHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.\r\n\r\nMitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.\r\n\r\nWhile plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.\r\n\r\nShmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.\r\n\r\nThe authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). \nSources: Literature",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:22:14.744423+11:00",
"panel_name": "Mitochondrial disease",
"panel_id": 203,
"panel_version": "0.510",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SHMT2 as ready",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:22:14.732808+11:00",
"panel_name": "Mitochondrial disease",
"panel_id": 203,
"panel_version": "0.510",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:22:10.916193+11:00",
"panel_name": "Mitochondrial disease",
"panel_id": 203,
"panel_version": "0.510",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SHMT2 as Green List (high evidence)",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:22:10.909194+11:00",
"panel_name": "Mitochondrial disease",
"panel_id": 203,
"panel_version": "0.510",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:21:42.693133+11:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.154",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SHMT2 as ready",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:21:42.685727+11:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.154",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:21:41.463227+11:00",
"panel_name": "Mitochondrial disease",
"panel_id": 203,
"panel_version": "0.509",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: SHMT2 was added\ngene: SHMT2 was added to Mitochondrial disease. Sources: Literature\nMode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SHMT2 were set to 33015733\nPhenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly\nReview for gene: SHMT2 was set to GREEN\nAdded comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.\r\n\r\nAll affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.\r\n\r\nBiallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. \r\n\r\nSHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.\r\n\r\nMitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.\r\n\r\nWhile plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.\r\n\r\nShmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.\r\n\r\nThe authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). \nSources: Literature",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:21:37.992884+11:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.154",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SHMT2 as Green List (high evidence)",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:21:37.985332+11:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.154",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:21:07.762557+11:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "0.153",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: SHMT2 was added\ngene: SHMT2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature\nMode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SHMT2 were set to 33015733\nPhenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly\nReview for gene: SHMT2 was set to GREEN\nAdded comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.\r\n\r\nAll affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.\r\n\r\nBiallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. \r\n\r\nSHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.\r\n\r\nMitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.\r\n\r\nWhile plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.\r\n\r\nShmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.\r\n\r\nThe authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). \nSources: Literature",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:19:05.761826+11:00",
"panel_name": "Cardiomyopathy_Paediatric",
"panel_id": 3270,
"panel_version": "0.18",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SHMT2 as ready",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:19:05.753811+11:00",
"panel_name": "Cardiomyopathy_Paediatric",
"panel_id": 3270,
"panel_version": "0.18",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:18:54.429304+11:00",
"panel_name": "Cardiomyopathy_Paediatric",
"panel_id": 3270,
"panel_version": "0.18",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SHMT2 as Green List (high evidence)",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:18:54.419009+11:00",
"panel_name": "Cardiomyopathy_Paediatric",
"panel_id": 3270,
"panel_version": "0.18",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:18:46.071203+11:00",
"panel_name": "Cardiomyopathy_Paediatric",
"panel_id": 3270,
"panel_version": "0.17",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: SHMT2 was added\ngene: SHMT2 was added to Cardiomyopathy_Paediatric. Sources: Literature\nMode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SHMT2 were set to 33015733\nPhenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly\nReview for gene: SHMT2 was set to GREEN\nAdded comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.\r\n\r\nAll affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.\r\n\r\nBiallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. \r\n\r\nSHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.\r\n\r\nMitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.\r\n\r\nWhile plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.\r\n\r\nShmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.\r\n\r\nThe authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). \nSources: Literature",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:18:28.700198+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.488",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SHMT2 as ready",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:18:28.689262+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.488",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:18:25.376455+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.488",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SHMT2 as Green List (high evidence)",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:18:25.368893+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.488",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:17:28.111543+11:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "0.487",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: SHMT2 was added\ngene: SHMT2 was added to Microcephaly. Sources: Literature\nMode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SHMT2 were set to 33015733\nPhenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly\nReview for gene: SHMT2 was set to GREEN\nAdded comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.\r\n\r\nAll affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.\r\n\r\nBiallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. \r\n\r\nSHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.\r\n\r\nMitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.\r\n\r\nWhile plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.\r\n\r\nShmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.\r\n\r\nThe authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). \nSources: Literature",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:11:09.137703+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4873",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SHMT2 as ready",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:11:09.120006+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4873",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:11:01.164725+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4873",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SHMT2 as Green List (high evidence)",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:11:01.154422+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4873",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:10:43.233623+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4872",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: SHMT2 was added\ngene: SHMT2 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SHMT2 were set to 33015733\nPhenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly\nReview for gene: SHMT2 was set to GREEN\nAdded comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.\r\n\r\nAll affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.\r\n\r\nBiallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. \r\n\r\nSHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.\r\n\r\nMitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.\r\n\r\nWhile plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.\r\n\r\nShmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.\r\n\r\nThe authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). \nSources: Literature",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:08:53.034351+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3063",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SHMT2 as ready",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:08:53.025781+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3063",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:08:47.716799+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3063",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SHMT2 as Green List (high evidence)",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T13:08:47.706369+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3063",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: shmt2 has been classified as Green List (High Evidence).",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-11T09:46:29.579117+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3062",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: ITFG2 was added\ngene: ITFG2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: ITFG2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z\nPhenotypes for gene: ITFG2 were set to Neurodevelopmental abnormality; Intellectual disability; Developmental regression; Ataxia\nPenetrance for gene: ITFG2 were set to Complete\nReview for gene: ITFG2 was set to AMBER\nAdded comment: ITFG2 was suggested to be a candidate gene for autosomal recessive ID in the study by Harripaul et al (2018 - PMID: 28397838). The authors performed microarray and exome sequencing in 192 consanguineous families and identified a homozygous ITGF2 stopgain variant (NM_018463.3:c.472G>T / p.Glu158*) along with 3 additional variants segregating with ID within an investigated family (PK51).\r\n\r\nCheema et al (2020 - https://doi.org/10.1038/s41525-020-00150-z) report briefly on a male, born to consanguineous parents presenting with NDD, seizures, regression and ataxia. There was a similarly affected female sibling. Evaluation of ROH revealed a homozygous ITFG2 nonsense variant [NM_018463.3:c.361C>T / p.(Gln121*)]. Families in this study were investigated by trio WES or WGS.\r\n\r\nEvaluation of data of the same lab revealed 3 additional unrelated subjects with overlapping phenotypes, notably NDD and ataxia. These individuals were - each - homozygous for pLoF variants [NM_018463.3:c.848-1G>A; NM_018463.3:c.704dupC, p.(Ala236fs), NM_018463.3:c.1000_1001delAT, p.(Ile334fs)].\r\n\r\nAs discussed in OMIM, ITFG2 encodes a subunit of the KICSTOR protein complex, having a role in regulating nutrient sensing by MTOR complex-1 (Wolfson et al 2017 - PMID : 28199306).\r\n\r\nPlease consider inclusion in the ID panel with amber rating, pending further details. \nSources: Literature",
"entity_name": "ITFG2",
"entity_type": "gene"
},
{
"created": "2020-10-11T08:44:30.172565+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.3062",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: SHMT2 was added\ngene: SHMT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SHMT2 were set to 33015733\nPhenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly\nPenetrance for gene: SHMT2 were set to Complete\nReview for gene: SHMT2 was set to GREEN\nAdded comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.\r\n\r\nAll affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.\r\n\r\nBiallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. \r\n\r\nSHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.\r\n\r\nMitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.\r\n\r\nWhile plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.\r\n\r\nShmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.\r\n\r\nThe authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).\r\n\r\nOverall this gene can be considered for inclusion with (probably) green rating in gene panels for ID, metabolic / mitochondrial disorders, cardiomyopathy, congenital microcephaly, corpus callosum anomalies, etc. \nSources: Literature",
"entity_name": "SHMT2",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:52:33.356418+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.78",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: IFT172 as ready",
"entity_name": "IFT172",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:52:33.348878+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.78",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ift172 has been classified as Green List (High Evidence).",
"entity_name": "IFT172",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:52:30.130262+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.78",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: IFT172 were changed from to Bardet-Biedl syndrome",
"entity_name": "IFT172",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:51:35.503504+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.77",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: IFT172 were set to ",
"entity_name": "IFT172",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:51:06.721938+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.76",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: IFT172 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "IFT172",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:50:18.707213+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.75",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MKS1 as ready",
"entity_name": "MKS1",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:50:18.695282+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.75",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mks1 has been classified as Green List (High Evidence).",
"entity_name": "MKS1",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:50:15.960048+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.75",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: MKS1 were changed from to Bardet-Biedl syndrome 13, MIM# 615990",
"entity_name": "MKS1",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:49:47.016635+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.74",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: MKS1 were set to ",
"entity_name": "MKS1",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:49:17.340284+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.73",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: MKS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "MKS1",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:48:36.287781+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.72",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: MKS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18327255, 24608809; Phenotypes: Bardet-Biedl syndrome 13, MIM# 615990; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "MKS1",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:45:50.073322+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.72",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: BBS9 as ready",
"entity_name": "BBS9",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:45:50.063265+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.72",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: bbs9 has been classified as Green List (High Evidence).",
"entity_name": "BBS9",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:45:46.612009+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.72",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: BBS9 were changed from to Bardet-Biedl syndrome 9, MIM#615986",
"entity_name": "BBS9",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:45:18.359035+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.71",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: BBS9 were set to ",
"entity_name": "BBS9",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:44:48.070975+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.70",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: BBS9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "BBS9",
"entity_type": "gene"
},
{
"created": "2020-10-10T19:44:16.986415+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.69",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: BBS9: Rating: GREEN; Mode of pathogenicity: None; Publications: 16380913, 22353939, 32686083, 32037757; Phenotypes: Bardet-Biedl syndrome 9, MIM#615986; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "BBS9",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:38:02.126598+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.69",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: BBS7 as ready",
"entity_name": "BBS7",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:38:02.116790+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.69",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: bbs7 has been classified as Green List (High Evidence).",
"entity_name": "BBS7",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:37:59.475454+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.69",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: BBS7 were changed from to Bardet-Biedl syndrome 7, MIM# 615984",
"entity_name": "BBS7",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:37:15.549462+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.68",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: BBS7 were set to ",
"entity_name": "BBS7",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:36:41.501546+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.67",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: BBS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "BBS7",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:36:12.440188+11:00",
"panel_name": "Bardet Biedl syndrome",
"panel_id": 53,
"panel_version": "0.66",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: BBS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 12567324, 21937992, 19797195; Phenotypes: Bardet-Biedl syndrome 7, MIM# 615984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "BBS7",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:19:47.661238+11:00",
"panel_name": "Syndromic Retinopathy",
"panel_id": 3099,
"panel_version": "0.103",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: EXOSC2 as ready",
"entity_name": "EXOSC2",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:19:47.652833+11:00",
"panel_name": "Syndromic Retinopathy",
"panel_id": 3099,
"panel_version": "0.103",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: exosc2 has been classified as Green List (High Evidence).",
"entity_name": "EXOSC2",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:19:45.493874+11:00",
"panel_name": "Syndromic Retinopathy",
"panel_id": 3099,
"panel_version": "0.103",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: EXOSC2 were changed from to Short stature, hearing loss, retinitis pigmentosa, and distinctive facies, MIM# 617763",
"entity_name": "EXOSC2",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:19:36.237124+11:00",
"panel_name": "Syndromic Retinopathy",
"panel_id": 3099,
"panel_version": "0.102",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: EXOSC2 were set to ",
"entity_name": "EXOSC2",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:19:26.370692+11:00",
"panel_name": "Syndromic Retinopathy",
"panel_id": 3099,
"panel_version": "0.101",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: EXOSC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "EXOSC2",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:17:12.949129+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4871",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: DHX38 as ready",
"entity_name": "DHX38",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:17:12.937783+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4871",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dhx38 has been classified as Amber List (Moderate Evidence).",
"entity_name": "DHX38",
"entity_type": "gene"
},
{
"created": "2020-10-10T18:17:06.053323+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.4871",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: DHX38 were changed from to Retinitis pigmentosa 84, MIM# 618220",
"entity_name": "DHX38",
"entity_type": "gene"
}
]
}