Research paper
Late onset muscular dystrophy with cerebral white matter changes due to partial merosin deficiency

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Abstract

Merosin-deficient congenital muscular dystrophy (CMD) is an autosomal recessive condition usually with onset at birth or within the first months of life. Affected children are severely disabled and usually do not achieve the ability to walk without support. They invariably have white matter abnormalities on brain magnetic resonance imaging (MRI). We report a 29-year-old man with a late childhood onset limb-girdle type muscular dystrophy and cerebral white matter changes on MRI. Immunocytochemical studies of the patient's muscle biopsy showed a reduction in expression of the laminin α2 chain of merosin. The patient had three affected siblings, and microsatellite genotyping confirmed linkage to the laminin α2 locus (LAMA2) on chromosome 6q2 in this family. This case probably represents a milder allelic variant of classical merosin-deficient CMD. Merosin status should be assessed in patients with late-onset limb girdle muscular dystrophy.

References (16)

  • V. Dubowitz
  • C.A. Sewry et al.

    Expression of laminin subunits in congenital muscular dystrophy

    Neuromuscular Disord.

    (1995)
  • C. Sewry et al.

    Diagnosis of merosin (laminin alpha-2) deficient congenital muscular dystrophy by skin biopsy

    Lancet

    (1996)
  • V. Dubowitz

    Muscle disorders of childhood

    (1995)
  • F.M.S. Tomé et al.

    Congenital muscular dystrophy with merosin deficiency

    C R Acad Sci Paris Life Sci

    (1994)
  • D. Hillaire et al.

    Localisation of merosin-negative congenital muscular dystrophy to chromosome 6q2 by homozygosity mapping

    Hum. Mol. Genet.

    (1994)
  • A. Helbling-Leclerc et al.

    Readjusting the localisation of merosin (laminin α2-chain) deficient congenital muscular dystrophy locus on chromosome 6q2

    C R Acad Sci Paris Life Sci

    (1995)
  • F. Schuler et al.

    Expression of laminin isoforms in mouse myogenic cells in vitro and in vivo

    J. Cell Sci.

    (1995)
There are more references available in the full text version of this article.

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