O#11   Towards the identification of a gene for the scalp-limited form of hypotrichosis simplex (HSS)

R.C. Betz1, Y.-A. Lee2, A. Bygum3, F. Brandrup3, J. Toribio4, A. Reis2, P. Propping1, S. Cichon1, M.M. Nothen1. 1 Institute of Human Genetics, University of Bonn, Bonn, Germany; 2 Gene Mapping Center, MDC, Berlin, Germany; 3 Dept of Dermatology, Odense University Hospital, Odense, Denmark; 4 Dept of Dermatology, University of Santiago de Compostela, Santiago de Compostela, Spain

Hypotrichosis simplex is a rare, autosomal-dominant form of isolated alopecia. A generalized form affecting all body hair can be distinguished from a scalp-limited form (HSS). Patients with the scalp-limited form experience a progressive, gradual loss of scalp hair, beginning at the middle of the first decade and leading to almost complete alopecia by the third decade. Of interest, the histological picture of scalp biopsies from patients with HSS show many features of androgenetic alopecia. Here, we describe the localization of the first hypotrichosis simplex locus and provide evidence that HSS maps to 6p21.3 in a Danish and a Spanish family. Blood samples from 62 individuals were collected, 27 of whom were affected. We performed a genomewide linkage analysis. Haplotype analysis of recombination events localized the disease gene to a 14.5 cM interval between markers D6S276 and D6S1607 with a maximum LOD score of 11.97 for both families. Recently, the region for HSS could further be narrowed down to an interval of ~ 2 cM. Screening of candidate genes is currently being performed and several candidate genes could be excluded by sequencing. The identification of the gene for HSS could offer the unique possibility to identifying factors that are not only necessary but also specific for hair growth. This may be important for our understanding of the molecular and cellular pathways that regulate growth of scalp hair. Furthermore, the mutated gene for HSS could illuminate our understanding of common androgenetic alopecia.