Mild POMGnT1 mutations underlie a novel limb-girdle muscular dystrophy variant.

Abstract

BACKGROUND:

Mutations in protein-O-mannose-beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) have been found in muscle-eye-brain disease, a congenital muscular dystrophy with structural eye and brain defects and severe mental retardation.

OBJECTIVE:

To investigate whether mutations in POMGnT1 could be responsible for milder allelic variants of muscular dystrophy.

DESIGN:

Screening for mutations in POMGnT1.

SETTING:

Tertiary neuromuscular unit.

PATIENT:

A patient with limb-girdle muscular dystrophy phenotype, with onset at 12 years of age, severe myopia, normal intellect, and decreased alpha-dystroglycan immunolabeling in skeletal muscle.

RESULTS:

A homozygous POMGnT1 missense mutation (c.1666G>A, p.Asp556Asn) was identified. Enzyme studies of the patient's fibroblasts showed an altered kinetic profile, less marked than in patients with muscle-eye-brain disease and in keeping with the relatively mild phenotype in our patient.

CONCLUSIONS:

Our findings widen the spectrum of disorders known to result from mutations in POMGnT1 to include limb-girdle muscular dystrophy with no mental retardation. We propose that this condition be known as LGMD2M. The enzyme assay used to diagnose muscle-eye-brain disease may not detect subtle abnormalities of POMGnT1 function, and additional kinetic studies must be carried out in such cases.

• Authors: Emma M Clement, Caroline Godfrey, Jenny Tan, Martin Brockington, Silvia Torelli, Lucy Feng, Susan C Brown, Cecilia Jimenez-Mallebrera, Caroline A Sewry, Cheryl Longman, Rachael Mein, Steve Abbs, Jiri Vajsar, Harry Schachter, Francesco Muntoni
• Journal: Archives of neurology (Arch Neurol) Vol. 65 Issue 1 Pg. 137-41 (Jan 2008) ISSN: 0003-9942 [Print] United States
• PMID: 18195152 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dystroglycans
• N-Acetylglucosaminyltransferases
• protein O-mannose beta-1,2-N-acetylglucosaminyltransferase

Topics

• Alleles
• Blotting, Western
• Child
• DNA Mutational Analysis
• Dystroglycans (metabolism)
• Fibroblasts (enzymology)
• Genetic Testing
• Humans
• Immunohistochemistry
• Kinetics
• Male
• Muscle, Skeletal (metabolism, pathology)
• Muscular Dystrophies, Limb-Girdle (complications, genetics, psychology)
• Mutation
• Mutation, Missense (genetics)
• Myopia (etiology)
• N-Acetylglucosaminyltransferases (genetics)
• Phenotype