P#08  The molecular basis of hereditary hypotrichosis simplex of the scalp

Etgar Levy-Nissenbaum, Moshe Frydman, Hadas Lahat, Tengiz Bakhan, Boleslaw Goldman and Elon Pras. Danek Gartner Institute of Human Genetics; Sheba Medical Center, Tel Hashomer, Israel; affiliated to the Sackler Faculty of Medicine, Tel Aviv University, , Israel

Hypotrichosis simplex of the scalp (HSS) is an autosomal dominant disorder that is manifested by loss of the scalp hair, equally affecting males and females. Affected individuals experience a gradual loss of hair between the ages of 5 and 12 and by the middle of their third decade only a few sparse short hairs are left on the scalp. The hair in other locations of the body remains intact. We have collected DNA samples from a large multi-generation Israeli Yemenite family. Linkage analysis in this family revealed that the disease-causing gene maps to chromosome 6p21.3. By identifying new polymorphic markers from within this interval we have reduced the gene interval to 11.6 Mb, a region known to contain about 250 transcripts. We embarked on a systematic study of all the genes from the interval that show strong expression in skin tissue and found a gene from within the linkage interval that is expressed exclusively in keratinocytes. We PCR-amplified and directly sequenced the entire coding region in one affected individual. In one of the genes from this region, we have identified a heterozygous substitution, resulting in the formation of a premature stop codon. Full segregation of the mutation was observed in the extended family, and screening of 750 control chromosomes identified only the wild type form. Currently, we are checking this gene in additional HSS families. Identification of the HSS gene, may shed light on new molecular pathways involved in human hair growth and human hair disorders.