BIN1 was first reported in relation to autosomal dominant centronuclear myopathy in 2014 (Böhm J, et al., 2014, PMID: 25260562). It is characterized by progressive adult-onset myopathy without facial weakness. Heterozygous ariants in the BIN1 gene have been reported in seven patients with autosomal dominant centronuclear myopathy in three publications (PMIDs: 25260562, 27854204, 29103045). Seven unique variants have been reported, falling into two types either missense or single amino acid deletions in the N-terminal amphipathic helix, where a dominant negative effect has been observed (PMID: 25260562), or frameshifts near the C-terminus which extend the protein and may impact SH3 domain folding or interaction with other proteins. This gene-disease relationship is further supported by its biochemical function in the t-tublue system (PMID: 31857086), enhanced expression in skeletal muscle (PMID: 9182667), protein-protein interaction with DNM2 (PMID: 15483625), and functional alteration in patient cells (Böhm J, et al., 2014, PMID: 25260562). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.
Of note, BIN1 has also been reported in relation to autosomal recessive centronuclear myopathy. Due to the proposed difference in mechanism, loss of function, those cases were considered in a separate curation.
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