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A homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy

Lookup NU author(s): Dr Katherine JohnsonORCiD, Lauren Phillips, Dr Ana TopfORCiD, Professor Volker StraubORCiD

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Abstract

© 2017 Elsevier B.V. Defects of O-linked glycosylation of alpha-dystroglycan cause a wide spectrum of muscular dystrophies ranging from severe congenital muscular dystrophy associated with abnormal brain and eye development to mild limb girdle muscular dystrophy. We report a female patient who developed isolated pelvic girdle muscle weakness and wasting, which became symptomatic at age 42. Exome sequencing uncovered a homozygous c.131T > G (p.Leu44Pro) substitution in DPM3, encoding dolichol-P-mannose (DPM) synthase subunit 3, leading to a 50% reduction of enzymatic activity. Decreased availability of DPM as an essential donor substrate for protein O-mannosyltransferase (POMT) 1 and 2 explains defective skeletal muscle alpha-dystroglycan O-glycosylation. Our findings show that DPM3 mutations may lead to an isolated and mild limb girdle muscular dystrophy phenotype without cardiomyopathy.

Publication metadata

Author(s): Van den Bergh PYK, Sznajer Y, Van Parys V, van Tol W, Wevers RA, Lefeber DJ, Xu L, Lek M, MacArthur DG, Johnson K, Phillips L, Topf A, Straub V

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2017

Volume: 27

Issue: 11

Pages: 1043-1046

Online publication date: 17/07/2017

Acceptance date: 12/07/2017

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/j.nmd.2017.07.006

DOI: 10.1016/j.nmd.2017.07.006

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