Prenatal diagnosis in merosin-deficient congenital muscular dystrophy

Prenatal diagnosis was carried out in five merosin-deficient congenital muscular dystrophy (CMD) families. We studied both laminin-alpha 2 chain expression in trophoblast using immunocytochemistry and linkage analysis to the LAMA2 locus. In four families there was good agreement between the immunocytochemistry and linkage analysis results: in one case the trophoblast was negative for LAMA2 expression and haplotype analysis suggested the foetus was affected; in the other three cases the laminin-alpha 2 chain expression was normal and foetuses were found to be carriers. In the remaining family, a case of partial laminin-alpha 2 chain expression, the immunostaining of the trophoblast was weaker compared to the control. Linkage analysis, however, could not be performed because of maternal DNA contamination. After termination of pregnancy, the foetal muscle was studied and suggested weak laminin-alpha 2 chain expression. The haplotype analysis however showed that the foetus was probably a carrier, unless a double recombinant event had occurred. We conclude that a combination of immunocytochemistry and linkage analysis can be used for the prenatal diagnosis of merosin deficient CMD. The results are easy to interpret in families with total absence of the protein, while caution is required when dealing with families where partial expression occurs.