SMARCE1 (the encoded protein is referred to as BAF57) was first reported in relation to autosomal dominant familial clear cell meningioma in 2013 by Smith et al., PMID:23377182. At least 9 unique variants (most inherited truncating variants often with a second variant (truncating or LOH in the tumor) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level and trio or pedigree data. Pedigrees reported thus far do not yield scorable segregation data, although autosomal dominant inheritance with incomplete penetrance (in males) is apparent in the familial studies reported. While there is no definitive penetrance estimation in literature and the mechanism of sex-biased penetrance is unknown, Smith et al PMID:23377182 notes that in a cohort of 13 individuals with clear cell spinal meningiomas from 9 families, 12 are female. A total of 11 points curated from 5 publications (PMIDS:23377182, 25143307, 26803492, 27891692, 30421029) are described. Experimental work shows lack of SMARCE1 expression in mengioma tumors (PMID:23377182, 27891692) as well as normal expression in non-tumor tissues with multiple isoforms expressed in brain and neuronal tissues (PMID:19245665). Reports display the role of BAF57 in CD4/CD8 regulation in T-cell lineage (PMID: 12110891), androgen (PMC:1061596) or estrogen (PMC:126156) receptor interaction, cell cycle regulation (PMID:16135788), and interaction with transcriptional repressors in neuronal progenitor cells (PMID: 31428904). However, functional studies in patient or non-patient cell lines, and animal models that directly relate to familial meningioma were not identified. Lomeli et al (PMID:27149204) provides a thorough review of BAF57 molecular and genetic studies up to 2016 and no further experimental studies directly relating to familial meningioma were identified between 2016 and present (2020). Currently the functional/causal roles of SMARCE1 in familial meningioma are overall experimentally unknown although a total of 2 pts were curated from 3 publications (PMIDS:23377182, 27891692, 19245665). Based on extensive genetic evidence as well as experimental expression evidence, and replication since the time of publication in 2013, SMARCE1 is definitively associated with autosomal dominant familial clear cell meningioma.
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