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Childhood onset hereditary spastic paraplegia v4.20 | MAG | Sarah Leigh Tag Q1_23_promote_green was removed from gene: MAG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v4.20 | MAG | Sarah Leigh changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosoma lfollowing NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v4.20 | MAG | Sarah Leigh reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v4.19 | MAG |
Sarah Leigh Source Expert Review Green was added to MAG. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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Childhood onset hereditary spastic paraplegia v3.18 | MAG | Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: MAG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v3.18 | MAG | Arina Puzriakova Publications for gene: MAG were set to 26179919; 24482476 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v3.17 | MAG | Arina Puzriakova Classified gene: MAG as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v3.17 | MAG |
Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least 12 individuals from 8 families have been identified with biallelic variants in this gene. Clinical features are characterised by spasticity (9/13), neuropathy (8/13), optic atrophy (7/13), variable cognitive deficits (7/13), and cerebellar signs (10/13) including ataxia in some (8/13) although 3/10 showed normal brain MRI results. |
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Childhood onset hereditary spastic paraplegia v3.17 | MAG | Arina Puzriakova Gene: mag has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v3.16 | MAG | Arina Puzriakova Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, 616680 to Spastic paraplegia 75, autosomal recessive, OMIM:616680 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v2.115 | IFIH1 |
Arina Puzriakova Added comment: Comment on list classification: Spasticity can be a prominent feature of Aicardi-Goutières syndrome (OMIM:615846) and has been reported as an early presenting sign in some cases. There has also been a case of spastic paraplegia without other common manifestations such as abnormal brain imaging and impaired cognitive development. Overall there is value in including IFIH1 on this panel and therefore this gene should be promoted to Green at the next GMS panel update. |
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Childhood onset hereditary spastic paraplegia v2.87 | PI4KA |
Ivone Leong changed review comment from: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. PMID: 25855803. From OMIM: "3 fetuses were all diagnosed in utero with multiple congenital anomalies resulting in the termination of pregnancy between 16 and 34 weeks' gestation. All fetuses had bilateral perisylvian polymicrogyria and cerebellar hypoplasia or dysplasia. One had a small pons. Additional features included severe talipes equinovarus, externally rotated hips, and variable contractures of the limbs or fingers." PMID:34415322. 10 patients from 10 unrelated families with biallelic varaints in PI4KA. Patients showed a spectrum of severe global neurodevelopmental delay (8/10 moderate to severe ID), hypomyelination, cerebellar hyoplasia (1/10), cerebellar atrophy (5/10), bilateral perisylvian polymicrogyria (1/10), immunological problems (hypogammaglobulinaemia, lymphopaenia, and autoimmune neutorpaenia - 4/10), bowl dysfunction (4/10). Age of onset ranged from newborn to 17 years. PMID: 34415310. 7 unrelated families. Family 1: Amish. Severe extensive multiple intestinal atresia, IBD and combined immunodeficiency (2/4). Families 3 - 8 all have 1 affected individual, (Turkish, Indian, German and Italian). Global developmental delay (all), ID (severe to mild), cerebellar and/or brainstem anomalies (3/6), spasticity (all), immature gyral pattern (1/6), leukodystrophy (6/6), multiple intestinal atresia (0/6), IBD (3/6), combined immunodeficiency (2/6). Early age of onset.; to: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. PMID: 25855803. From OMIM: "3 fetuses were all diagnosed in utero with multiple congenital anomalies resulting in the termination of pregnancy between 16 and 34 weeks' gestation. All fetuses had bilateral perisylvian polymicrogyria and cerebellar hypoplasia or dysplasia. One had a small pons. Additional features included severe talipes equinovarus, externally rotated hips, and variable contractures of the limbs or fingers." PMID:34415322. 10 patients from 10 unrelated families with biallelic varaints in PI4KA. Patients showed a spectrum of severe global neurodevelopmental delay (8/10 moderate to severe ID), hypomyelination, cerebellar hyoplasia (1/10), cerebellar atrophy (5/10), bilateral perisylvian polymicrogyria (1/10), immunological problems (hypogammaglobulinaemia, lymphopaenia, and autoimmune neutorpaenia - 4/10), bowl dysfunction (4/10). Age of onset ranged from newborn to 17 years. PMID: 34415310. 7 unrelated families. Family 1: Amish. Severe extensive multiple intestinal atresia, IBD and combined immunodeficiency (2/4). Families 3 - 8 all have 1 affected individual, (Turkish, Indian, German and Italian). Global developmental delay (all), ID (severe to mild), cerebellar and/or brainstem anomalies (3/6), spasticity (all), immature gyral pattern (1/6), leukodystrophy (6/6), multiple intestinal atresia (0/6), IBD (3/6), combined immunodeficiency (2/6). Early age of onset. |
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Childhood onset hereditary spastic paraplegia v2.15 | MAG | Zornitza Stark reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 26179919, 31402626, 32629324; Phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.166 | MAG | Louise Daugherty commented on gene: MAG: Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.164 | MAG | Louise Daugherty Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.75 | MAG | Louise Daugherty Source Yorkshire and North East GLH was added to MAG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.74 | MAG | Nick Beauchamp reviewed gene: MAG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.74 | MAG | Louise Daugherty commented on gene: MAG: Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.60 | MAG |
Louise Daugherty commented on gene: MAG: Amber rating on Hereditary spastic paraplegia panel 1.198 Comment on list classification: Updated rating from Grey to Amber: Gene added and rated red by Chris Buxton (Bristol NHS) based on 1 family in PMID:24482476. One additional family reported in PMID:26179919 but require at least one further case for diagnostic rating. Rebecca Foulger (Genomics England curator), 18 Dec 2018 In 3 siblings with AR spastic paraplegia born of consanguineous Palestinian parents, Lossos et al. (2015, PMID:26179919) identified a homozygous c.399C-G transversion in the MAG gene (S133R). Rebecca Foulger (Genomics England curator), 18 Dec 2018 PMID:24482476 (Novarino et al 2014) identified MAG as a HSP candidate gene based on the HSPome (network analysis). In 2 affected sisters from a consanguineous family (family 1226) with AR spastic paraplegia-75, PMID:24482476 identified homozygosity for a c.1288T-G transversion in the MAG gene (C430G). Rebecca Foulger (Genomics England curator), 18 Dec 2018 1 family Novarino (2014, 24482476). Homozygous Cys430Gly with HSp phenotype. No other detail. 1 family. Limited evidence Diagnostic on Sheffield HSP panel Sources: Literature Chris Buxton (North Bristol NHS Trust), 27 Nov 2018. Submitted Red rating. |
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Childhood onset hereditary spastic paraplegia v1.60 | MAG | Louise Daugherty Classified gene: MAG as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.60 | MAG | Louise Daugherty Gene: mag has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.48 | MAG | Louise Daugherty reviewed gene: MAG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.41 | MAG | Louise Daugherty Classified gene: MAG as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.41 | MAG | Louise Daugherty Gene: mag has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.6 | MAG | James Polke reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spastic paraplegia 75, autosomal recessive, 616680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.5 | MAG | Louise Daugherty Source NHS GMS was added to MAG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.4 | MAG | Louise Daugherty Source London North GLH was added to MAG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Childhood onset hereditary spastic paraplegia v1.3 | MAG |
Louise Daugherty Added phenotypes Spastic paraplegia 75, autosomal recessive, 616680 for gene: MAG Publications for gene MAG were changed from 24482476; 26179919 to 26179919; 24482476 |
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Childhood onset hereditary spastic paraplegia v0.6 | MAG |
Sarah Leigh gene: MAG was added gene: MAG was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Amber,Literature Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAG were set to 24482476; 26179919 Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, 616680 |