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Neuromuscul Disord. 2014 Apr;24(4):312-20. doi: 10.1016/j.nmd.2014.01.001. Epub 2014 Jan 11.

A novel missense mutation in POMT1 modulates the severe congenital muscular dystrophy phenotype associated with POMT1 nonsense mutations.

Author information

1
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, United States; Seattle Children's Hospital, Seattle, WA, United States.
2
Department of Laboratories, Seattle Children's Hospital, Seattle, WA, United States.
3
Prevention Genetics, Marshfield, WI, United States.
4
Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
5
Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
6
Department of Neurosciences University of California, San Diego, La Jolla, CA, United States; Department of Pediatrics, University of California, San Diego, La Jolla, CA, United States; Rady Children's Hospital San Diego, CA, United States.
7
Department of Pathology, Seattle Children's Hospital, Seattle, WA, United States.
8
Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States; Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States; Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
9
Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
10
Department of Neurology, University of Washington, Seattle, WA, United States; Department of Pediatrics, University of Washington, Seattle, WA, United States; Seattle Children's Hospital, Seattle, WA, United States. Electronic address: sgospe@uw.edu.

Abstract

Mutations in POMT1 lead to a group of neuromuscular conditions ranging in severity from Walker-Warburg syndrome to limb girdle muscular dystrophy. We report two male siblings, ages 19 and 14, and an unrelated 6-year old female with early onset muscular dystrophy and intellectual disability with minimal structural brain anomalies and no ocular abnormalities. Compound heterozygous mutations in POMT1 were identified including a previously reported nonsense mutation (c.2167dupG; p.Asp723Glyfs*8) associated with Walker-Warburg syndrome and a novel missense mutation in a highly conserved region of the protein O-mannosyltransferase 1 protein (c.1958C>T; p.Pro653Leu). This novel variant reduces the phenotypic severity compared to patients with homozygous c.2167dupG mutations or compound heterozygous patients with a c.2167dupG mutation and a wide range of other mutant POMT1 alleles.

KEYWORDS:

Congenital muscular dystrophy; Dystroglycanopathy; Limb girdle muscular dystrophy; POMT1; Protein O-mannosylation; Walker–Warburg syndrome

PMID:
24491487
PMCID:
PMC3959257
DOI:
10.1016/j.nmd.2014.01.001
[Indexed for MEDLINE]
Free PMC Article

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