Selected paper from the 1st International Congress of the World Muscle Society
Variable clinical phenotype in merosin-deficient congenital muscular dystrophy associated with differential immunolabelling of two fragments of the laminin α2 chain

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Abstract

Approximately half the cases of classical congenital muscular dystrophy (CMD) have a pronounced deficiency or absence of the laminin α2 chain of laminin-2 (merosin). This is caused by mutations in the LAMA2 gene that codes for laminin α2, and all informative cases so far studied show linkage to the appropriate region on chromosome 6q. Most CMD patients with a deficiency of laminin α1 have a severe phenotype that involves skeletal muscle, and the central and peripheral nervous system. We have identified four cases that have a severe reduction of laminin α2 using a commercial antibody that only recognises a C-terminal 80 kDa fragment, but show a pronounced reduction using an antibody to the 300 kDa fragment. Haplotype analysis is compatible with linkage to the LAMA2 locus in three informative families, whilst the fourth family was not informative. Two of the affected children are ambulant and have a mild phenotype. The third case is unusual in having severe muscle weakness but does not show the white matter changes on magnetic resonance imaging of the brain that is usually seen in merosin-deficient cases of CMD; the fourth case has a severe phenotype, typical of merosin-deficient patients but shows good immunolabelling of the 80 kDa fragment of laminin α2, corresponding to the C-terminal region. Our data show that there is a broad spectrum of phenotype and protein expression associated with a primary deficiency in laminin α2, and that a wider range of clinical cases need to be screened for a deficiency of merosin. It is also important to study the expression of laminin α2 with more than one antibody.

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