CLINICAL AND GENETIC-HETEROGENEITY IN MECKEL-SYNDROME

Meckel syndrome (MKS) is a lethal malformation syndrome characterised by posterior meningoencephalocele, polycystic kidneys, fibrotic change s of the liver, and polydactyly. We have previously shown a linkage to chromosome 17q in 17 Finnish Meckel families. In this study we have a nalysed one Italian, one Austrian (of Turkish origin) and three Britis h MKS families (Caucasian, Pakistani, and Bangladeshi families) for li nkage to the MKS locus on chromosome 17q22-q24. We did not observe co- segregation of the disease and marker haplotypes in the Austrian famil y or in the three British families, of which two represented classical MKS and one a slightly atypical MKS phenotype with longer survival of the patient. In the Italian family the affected and non-affected chil dren did not share the same maternal chromosome and thus this family c ould represent the same allelic disease as the Finnish MKS families. T hese results suggest locus heterogeneity in Meckel syndrome - a featur e previously suspected based on the highly variable clinical phenotype .