Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation

Neuromuscul Disord. 2009 May;19(5):352-6. doi: 10.1016/j.nmd.2009.03.001. Epub 2009 Apr 1.

Abstract

The dystroglycanopathies comprise a clinically and genetically heterogeneous group of muscular dystrophies characterized by deficient glycosylation of alpha-dystroglycan. Mutations in the fukutin (FKTN) gene have primarily been identified among patients with classic Fukuyama congenital muscular dystrophy (FCMD), a severe form of dystroglycanopathy characterized by CMD, cobblestone lissencephaly and ocular defects. We describe two brothers of Caucasian and Japanese ancestry with normal intelligence and limb-girdle muscular dystrophy (LGMD) due to compound heterozygous FKTN mutations. Muscle biopsy showed a dystrophy with selectively reduced alpha-dystroglycan glycoepitope immunostaining. Immunoblots revealed hypoglycosylation of alpha-dystroglycan and loss of laminin binding. FKTN gene sequencing identified two variants: c.340G>A and c.527T>C, predicting missense mutations p.A114T and p.F176S, respectively. Our results provide further evidence for ethnic and allelic heterogeneity and the presence of milder phenotypes in FKTN-dystroglycanopathy despite a substantial degree of alpha-dystroglycan hypoglycosylation in skeletal muscle.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Asian / genetics
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Dystroglycans / metabolism
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Glycosylation
  • Humans
  • Intellectual Disability / genetics
  • Laminin / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophies, Limb-Girdle / ethnology
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Muscular Dystrophies, Limb-Girdle / metabolism
  • Mutation / genetics*
  • Mutation, Missense / genetics
  • White People

Substances

  • DAG1 protein, human
  • FKTN protein, human
  • Genetic Markers
  • Laminin
  • Membrane Proteins
  • Dystroglycans