Symptomatic heterozygous X-Linked myotubular myopathy female patient with a large deletion at Xq28 and decrease expression of normal allele

X-linked myotubular myopathy (XLMTM; OMIM 310400) is a centronuclear congenital muscular disorder of Xlinked recessive inheritance. Although female carriers are typically asymptomatic, affected heterozygous females have been described. Here, we describe the case of a sporadic female patient with suspicion of centronuclear myopathy and a heterozygous large deletion at Xq28 encompassing the MAMLD1, MTM1, MTMR1, CD99L2, and HMGB3 genes. The deletion was first detected using a custom next generation sequencing (NGS)-based multigene panel and finally characterized by comparative genomic hybridization array and multiplex ligation probe assay techniques. In this patient we have confirmed, by MTM1 mRNA quantification, a MTM1 gene expression less than the expected 50 percent in patient muscle. The significant 20% reduction in MTM1 mRNA expression in muscle, precludes low level of the normal myotubularin protein as the cause of the phenotype in this heterozygous female. We have also found that BIN1 expression in patient muscle biopsy was significantly increased, and postulate that BIN1 expression will be increased in XLMTM patient muscle as an attempt to maintain muscle function.

Automated summary

X-linked myotubular myopathy is a centronuclear muscle disorder with X-linked recessive inheritance, characterized by severe muscle weakness. It is most commonly seen in males, but can also affect females. A female patient was identified with a large deletion encompassing multiple genes on the X chromosome, leading to reduced MTM1 gene expression and potentially increased BIN1 expression related to muscle function maintenance.