THE GENE RESPONSIBLE FOR CLOUSTON HIDROTIC ECTODERMAL DYSPLASIA MAPS TO THE PERICENTROMERIC REGION OF CHROMOSOME 13Q

Hidrotic ectodermal dysplasia (HED), Clouston type, is an autosomal do minant skin disorder which is most common in the French-Canadian popul ation and is characterized by hair defects, nail dystrophy and palmopl antar hyperkeratosis. Biophysical and biochemical studies conducted in HED suggested a molecular abnormality of keratins, We tested eight Fr ench-Canadian families segregating HED for linkage to microsatellite m arkers flanking the known keratin genes and were able to exclude linka ge to these loci, Therefore, a genome-wide search for the HED gene was initiated, The first lod score above 3.00 was obtained with the marke r D13S175 located in the pericentromeric region of chromosome 13q (Z(m ax) = 8.12 at zero recombination), The cumulative lod scores were abov e 3.00 for six other markers in the region. A multipoint linkage analy sis using the markers D13S175, D13S141 and D13S143 gave a maximum lod score of 11.12 at D13S141 with the one-led-unit support interval spann ing a 12.7 cM region which includes D13S175 and D13S141. Haplotype ana lysis allowed us to establish D13S143 as the telomeric flanking marker for the HED candidate region.