REFINED MAPPING OF THE COHEN-SYNDROME GENE BY LINKAGE DISEQUILIBRIUM

The Cohen syndrome is a rare autosomal recessively inherited disorder. Contrary to many case reports published elsewhere, the phenotype is u niform in Finland including nonprogressive ire mental and motor retard ation, typical dysmorphic features, granulocytopenia and marked ophtha lmological changes. By linkage analysis in five Finnish multiplex nucl ear families, the COH1 locus for the Cohen syndrome was recently assig ned to a 10-cM region between loci D8S270 and D8S521 on the long arm o f chromosome 8. Here we present results of linkage disequilibrium and haplotype analysis in an extended panel of 16 Finnish COH1 families us ing new markers localized in the COH1 region. By inferring historical recombinations in conserved haplotypes the COH1 gene was assigned in t he region of marker loci D8S1808, D8S1762 and D8S546. Calculations of genetic distances based on linkage disequilibrium suggest that the mos t likely localization of COH1 is in the immediate vicinity of marker l ocus D8S1762. Haplotype analysis suggests the occurrence of one main C OH1 mutation and possibly one or two rare ones in Finland. This inform ation will be useful in the positional cloning of the gene.