Open AccessThree novel MTM1 pathogenic variants identified in Japanese patients with X‐linked myotubular myopathy
Author(s) -
Nishikawa Atsuko,
Iida Aritoshi,
Hayashi Shinichiro,
Okubo Mariko,
Oya Yasushi,
Yamanaka Gaku,
Takahashi Ikuko,
aka Ikuya,
Noguchi Satoru,
Nishino Ichizo
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.621
Subject(s) - hypotonia , congenital myopathy , pathological , genetics , phenotype , medicine , muscle weakness , weakness , gene , bioinformatics , pathology , biology , muscle biopsy , anatomy , biopsy
Background X‐linked myotubular myopathy (XLMTM) is a form of the severest congenital muscle diseases characterized by marked muscle weakness, hypotonia, and feeding and breathing difficulties in male infants. It is caused by mutations in the myotubularin gene ( MTM1 ). Methods Evaluation of clinical history and examination of muscle pathology of three patients and comprehensive genome analysis on our original targeted gene panel system for muscular diseases. Results We report three patients, each of whom presents distinct muscle pathological features. The three patients have novel hemizygous MTM1 variants, including c.527A>G (p.Gln176Arg), c.595C>G (p.Pro199Ala), or c.688T>C (p.Trp230Arg). Conclusions All variants were assessed as “Class 4 (likely pathogenic)” on the basis of the guideline of American College of Medical Genetics and Genomics. These distinct pathological features among the patients with variants in the second cluster of PTP domain in MTM1 provides an insight into microheterogeneities in disease phenotypes in XLMTM.