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

Eur J Med Genet. 2021 Feb 19:104170. doi: 10.1016/j.ejmg.2021.104170. Online ahead of print.ABSTRACTX-linked myotubular myopathy (XLMTM; OMIM 310400) is a centronuclear congenital muscular disorder of X-linked 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.PMID:33618039 | DOI:10.1016/j.ejmg.2021.104170

Source: European Journal of Medical Genetics - February 22, 2021 Category: Genetics & Stem Cells Authors: Clara G ómez-González Roc ío Rosas Carlos Rodr íguez-Antolín Alvaro Garc ía-Guede Inmaculada Ib áñez de Caceres Javier Sanguino Samuel I Pascual Isabel Esteban Angela Del Pozo Mar ía Ángeles Mori Rosa J Torres Carmen Prior Source Type: research