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Emma M. Clement, MB, ChB; Caroline Godfrey, BSc; Jenny Tan, PhD; Martin Brockington, BSc; Silvia Torelli, PhD; Lucy Feng, PhD; Susan C. Brown, PhD; Cecilia Jimenez-Mallebrera, PhD; Caroline A. Sewry, PhD; Cheryl Longman, MD; Rachael Mein, BSc; Steve Abbs, PhD; Jiri Vajsar, MD; Harry Schachter, MD, PhD; Francesco Muntoni, MD

Arch Neurol. 2008;65(1):137-141.

Background  Mutations in protein-O-mannose-β1,2-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 -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.

Author Affiliations: Dubowitz Neuromuscular Unit, Department of Paediatrics, Hammersmith Hospital, Imperial College London (Drs Clement, Torelli, Feng, Brown, Jimenez-Mallebrera, Sewry, Longman, and Muntoni), Ms Godfrey, Mr Brockington, and DNA Laboratory, Genetics Centre, Guy's Hospital (Mss Godfrey and Mein and Dr Abbs), London, and Centre for Inherited Neuromuscular Disorders, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry (Dr Sewry), England; and Department of Structural Biology and Biochemistry (Drs Tan and Schachter) and Division of Neurology (Dr Vajsar), Hospital for Sick Children, and Faculty of Medicine, University of Toronto (Drs Vajsar and Schachter), Toronto, Ontario, Canada.

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