MYSM1 was first reported in relation to autosomal recessive bone marrow syndrome in 2013 (Alsultan et al., PMID: 24288411). Bone marrow failure due to MYSM1 deficiency is characterized by anemia, leukopenia, thrombocytopenia, and B cell deficiency resulting in recurrent infections and in some cases, non hematologic features such as dysmorphic features, skeletal abnormalities, and developmental delay. At least seven variants (e.g. missense, nonsense, frameshift, and canonical splice) that have been reported in seven probands in seven publications (PMIDs: 24288411, 28115216, 26220525, 33858043, 30735661, 32640305, 35295078) are included in this curation. MYSM1 variants segregated with disease in two families and heterozygous carriers were asymptomatic (PMIDs: 28115216, 24288411). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is also supported by mouse models, in vivo genetic reversion in an affected patient, biochemical function, functional alteration, and protein interactions studies. (PMIDs: 26125289, 26474655, 22184403, 26220525, 28115216). In summary, there is definitive evidence supporting the relationship between MYSM1 and autosomal recessive bone marrow failure. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen SCID-CID GCEP on June 7, 2024 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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