An autosomal dominant form of hereditary hypotrichosis simplex maps to 18p11.32-p11.23 in an Italian family

We report on a three-generation Italian family with dominant transmission of a form of hereditary hypotrichosis simplex (HHS). The nine affected adults presented with sparse, thin and short hair. Somewhat less sparse and longer hair was observed in the two affected young children in the third generation. Reduced hair growth affected the scalp and body, although normal eyelashes, eyebrows and growth of men's beards were observed. No associated abnormality was detected and the overall psychomotor development of the affected individuals was normal. A phenotypic variation was observed amongst the family members and is suggestive of a reduced penetrance of the trait or the effect of a modifying factor. After exclusion, in our family, of linkage to loci previously described in other forms of atrichia or hypotrichosis, we performed a genome-wide linkage analysis, which resulted in a positive lod score at 18p11.32-p11.23. We defined a critical region of about 35 cM flanked by markers D18S853 and D18S40. The highest two-point lod score was obtained with the microsatellite markers D18S1376, D18S53 and D18S453 (lod score of 3.31 at theta = 0.00). The 18p11.32-p11.23 locus represents the first chromosome region shown to be associated with hereditary hypotrichosis simplex.