Archives of neurology · 2008
Mild POMGnT1 mutations underlie a novel limb-girdle muscular dystrophy variant.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Clement Emma M, Godfrey Caroline, Tan Jenny, Brockington Martin, Torelli Silvia, Feng Lucy, Brown Susan C, Jimenez-Mallebrera Cecilia, Sewry Caroline A, Longman Cheryl, Mein Rachael, Abbs Steve, Vajsar Jiri, Schachter Harry, Muntoni Francesco
Аннотация
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.
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.