Work

A Deep Intronic Variant Activates a Pseudoexon in the MTM1Gene in a Family with X-Linked Myotubular Myopathy

Year: 2020

Type: article

Abstract: We report a novel intronic variant in the MTM1 gene in four males in a family with severe X-linked myotubular myopathy. The A>G variant in deep intronic space activates a cryptic 5’ donor splice site resulting in the inclusion of a 48bp pseudoexon into the mature MTM1 mRNA. The variant is present in all affected males, absent in unaffected males and heterozygous in the mother of the affected males. The included intronic sequence contains a premature stop codon and experiments using a translational inhibitor indicate that the mutant mRNAs undergo nonsense-mediate decay. We conclude that affected males produce no, or low, levels of myotubularin-1 protein leading to a severe neonatal myopathy. The study highlights the need to consider non-coding variants in genomic screening in families with X-linked myotubular myopathy.

Source: Molecular Syndromology

DOI: 10.1159/000510286

Authors: Jamie Fitzgerald, Cori Feist, Paula Dietz, Stephen Moore, Donald Basel

Institutions: Henry Ford Health, Oregon Health & Science University, Henry Ford Hospital, Medical College of Wisconsin

Language: English

Topic: Genomics and Rare Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases