Is there selection in favour of heterozygotes in families with merosin-deficient congenital muscular dystrophy?

Merosin-deficient congenital muscular dystrophy is an autosomal recessive n euromuscular disorder caused by partial or total absence of laminin-2 (mero sin) in the skeletal muscle. Affected children have severe weakness. hypoto nia at birth, high creatine kinase (CK) levels (more than 10 times normal) and are not able to walk or stand unsupported. Linkage and mutation analysi s demonstrated that the gene encoding for the laminin-alpha 2 chain, mapped on chromosome 6q22-23, is invariably responsible for this form of congenit al muscular dystrophy. We investigated the pattern of inheritance of the ha plotypes associated with the mutated allele in 29 informative merosin-defic ient families, using tightly linked informative polymorphic microsatellite markers. This allowed us to identify heterozygous individuals from normal h omozygotes, who are clinically, pathologically and biochemically indistingu ishable. By linkage analysis, we found a statistically significant increase in the number of heterozygous individuals carrying either the paternal or the maternal haplotypes associated with the mutated allele. This could sugg est a selection in favour of the alleles carrying mutations at the laminin alpha 2-chain locus.