Three novel MTM1 pathogenic variants identified in Japanese patients with X‐linked myotubular myopathy. Issue 5 (18th March 2019)

• Record Type: Journal Article
• Authors: Nishikawa, Atsuko; Iida, Aritoshi; Hayashi, Shinichiro; Okubo, Mariko; Oya, Yasushi; Yamanaka, Gaku; Takahashi, Ikuko; Nonaka, Ikuya; Noguchi, Satoru; Nishino, Ichizo
• Is Part Of: Molecular genetics & genomic medicine. Volume 7:Issue 5(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-03-18
• Subjects: MTM1 -- novel variants -- targeted gene panel system -- X‐linked myotubular myopathy; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.621
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: 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. Abstract : X‐linked myotubular myopathy (XLMTM) is among the most severe congenital muscle diseases characterized by marked muscle weakness, hypotonia, and feeding and breathing difficulties in male infants. We report three novel hemizygous MTM1 pathogenic variants, including c.527A>G (p.Gln176Arg), c.595C>G (p.Pro199Ala), and c.688T>C (p.Trp230Arg).