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Arch Neurol. 2008 Jan;65(1):137-41. doi: 10.1001/archneurol.2007.2.

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

Author information

1
Dubowitz Neuromuscular Unit, Department of Paediatrics, Hammersmith Hospital, Imperial College London, Du Cane Road, London W12 ONN, England.

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.

PMID:
18195152
DOI:
10.1001/archneurol.2007.2
[Indexed for MEDLINE]

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