title: 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.
  
  
  METHODS
  Screening for mutations in POMGnT1.
  
  
  METHODS
  Tertiary neuromuscular unit.
  
  
  METHODS
  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.affiliation: Dubowitz Neuromuscular Unit, Department of Paediatrics, Hammersmith Hospital, Imperial College London, Du Cane Road, London W12 ONN, England.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Clement
authors.forename: Caroline
authors.initials: C
authors.lastname: Godfrey
authors.forename: Jenny
authors.initials: J
authors.lastname: Tan
authors.forename: Martin
authors.initials: M
authors.lastname: Brockington
authors.forename: Silvia
authors.initials: S
authors.lastname: Torelli
authors.forename: Lucy
authors.initials: L
authors.lastname: Feng
authors.forename: Susan C
authors.initials: SC
authors.lastname: Brown
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jimenez-Mallebrera
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sewry
authors.forename: Cheryl
authors.initials: C
authors.lastname: Longman
authors.forename: Rachael
authors.initials: R
authors.lastname: Mein
authors.forename: Steve
authors.initials: S
authors.lastname: Abbs
authors.forename: Jiri
authors.initials: J
authors.lastname: Vajsar
authors.forename: Harry
authors.initials: H
authors.lastname: Schachter
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000483:Alleles; D015153:Blotting, Western; D002648:Child; D004252:DNA Mutational Analysis; D049030:Dystroglycans / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000150:complications / Q000235:genetics* / Q000523:psychology; D009154:Mutation; D020125:Mutation, Missense / Q000235:genetics; D009216:Myopia / Q000209:etiology; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D010641:Phenotype
chemical_list: D049030:Dystroglycans; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase