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Early onset or syndromic epilepsy v1.191 | MAST1 | Rebecca Foulger Source Wessex and West Midlands GLH was added to MAST1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.190 | MAST1 | Rebecca Foulger Source NHS GMS was added to MAST1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.189 | MAST1 | Rebecca Foulger edited their review of gene: MAST1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Red. ; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.188 | MAST1 | Tracy Lester reviewed gene: MAST1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations, 618273; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1532 | MAST1 | Sarah Leigh Marked gene: MAST1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1532 | MAST1 | Sarah Leigh Added comment: Comment when marking as ready: Based on reviewers' comments. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1532 | MAST1 | Sarah Leigh Gene: mast1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1520 | MAST1 | Rebecca Foulger commented on gene: MAST1: Added 'watchlist' tag. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1520 | MAST1 | Rebecca Foulger Tag watchlist tag was added to gene: MAST1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1520 | MAST1 | Rebecca Foulger Classified gene: MAST1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1520 | MAST1 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Amber. 6 individuals in PMID:30449657 with MAST1 variants, and seizures in 2/6 patients. DDD participant DDD4K.02310 has a synonymous variant in RXRG and a missense variant in MAST (Supplementary material of PMID:28135719). 1 individual in PMID:23934111 (Epi4K encephalopathies) had seizures- listed as benign variant from Polyphen in the paper tables. The phenotype appears complex, and MAST1 is not yet linked to epilepsy in OMIM, and is not yet on the DD-G2P list. Therefore rated as Amber awaiting further confirmed cases from the literature or clinic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1520 | MAST1 | Rebecca Foulger Gene: mast1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1488 | MAST1 |
Konstantinos Varvagiannis gene: MAST1 was added gene: MAST1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MAST1 were set to 30449657; 23934111 Phenotypes for gene: MAST1 were set to Global developmental delay, Intellectual disability, Abnormality of the corpus callosum, Cerebellar hypoplasia, Abnormality of the cerebral cortex, Seizures; Global developmental delay, Intellectual disability, Microcephaly, Autism, Seizures Penetrance for gene: MAST1 were set to unknown Review for gene: MAST1 was set to GREEN Added comment: PMID: 30449657 reports on 6 unrelated individuals with de novo mutations in MAST1. All these 6 individuals were investigated for a strikingly similar phenotype of enlarged corpus callosum (CC), cerebellar hypoplasia, cortical malformation with associated DD/ID. Seizures were a feature in 2/6 (one further had EEG anomalies without clinical seizures). Three of them harbored an in-frame deletion of 1 amino-acid (3 different indels reported - all in a specific domain) while 3 others had a missense variant (NM_014975.2:c.1549G>A or p.Gly517Ser). Mast1 has embryonic expression in murine models with postnatal decrease. Similarly qPCR of human fetal brain cDNA demonstrated expression at 13 and 22 gestational weeks. A murine model for L278del recapitulated the brain (incl. CC) and cerebellar phenotype while Mast1 knockout mice do not present similar morphological defects. While Western blot in murine brain lysates demonstrated absence of Mast1 in knockout and reduction in the L278del, Mast1 transcript levels for L278del were similar to wildtype. Other Mast proteins (Mast1 & Mast2) were significantly reduced upon western blot while this was not reflected in their mRNA levels, suggesting a dominant-negative effect, at least for the L278del. 4 additional individuals with somewhat different phenotype consisting DD/ID and microcephaly/autism are described in the supplement. All 4 had de novo missense variants but did not display the CC-cerebral and cerebellar anomalies. Four different (additional to Gly517Ser) missense SNVs were observed. Several additional individuals exist in the denovo-db (among others DDD participant DDD4K.02310 published in 28135719, 25666757 - McMichael et al. commented in the article, 27479843, etc.). [http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=Mast1] Epilepsy was a feature in 4/10 individuals (with an additional one with EEG anomalies without clinical seizures). One further individual from PMID:23934111 (in denovo-db) had seizures. As the authors comment (and as evident from the 6+4 reported patients) the related neurodevelopmental phenotype may be more complex. MAST1 is not related to any phenotype in G2P, nor in OMIM. As a result, this gene can be considered for inclusion in this panel as green (or amber). Sources: Literature |