M. Brockington et al., Assignment of a form of congenital muscular dystrophy with secondary merosin deficiency to chromosome 1q42, AM J HU GEN, 66(2), 2000, pp. 428-435
Citations number
33
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
We have previously reported an autosomal recessive form of congenital muscu
lar dystrophy, characterized by proximal girdle weakness, generalized muscl
e hypertrophy, rigidity of the spine, and contractures of the tendo Achille
s, in a consanguineous family from the United Arab Emirates. Early respirat
ory failure resulting from severe diaphragmatic involvement was present. In
tellect and the results of brain imaging were normal. Serum creatine kinase
levels were grossly elevated, and muscle-biopsy samples showed dystrophic
changes. The expression of the laminin-alpha 2 chain of merosin was reduced
on several fibers, but linkage analysis excluded the LAMA2 locus on chromo
some 6q22-23. Here, we report the results of genomewide linkage analysis of
this family, by use of homozygosity mapping. In all four affected children
, an identical homozygous region was identified on chromosome 1q42, spannin
g 6-15 cM between flanking markers D1S2860 and D1S2800. We have identified
a second German family with two affected children having similar clinical a
nd histopathological features; they are consistent with linkage to the same
locus. The cumulative LOD score was 3.57 (theta = .00) at marker D1S213. T
his represents a novel locus for congenital muscular dystrophy. We suggest
calling this disorder "CMD1B.'' The expression of three functional candidat
e genes in the CMD1B critical region was investigated, and no detectable ch
anges in their level of expression were observed. The secondary reduction i
n laminin-alpha 2 chain in these families suggests that the primary genetic
defect resides in a gene coding for a protein involved in basal lamina ass
embly.