Linkage of Marie-Unna hypotrichosis locus to chromosome 8p21 and exclusionof 10 genes including the hairless gene by mutation analysis

Marie-Unna hypotrichosis (MU) is a rare autosomal dominant congenital alope cia characterised by progressive hair loss starting in early childhood, oft en aggravated at puberty and leading to scarring alopecia of variable sever ity. We have studied three multigeneration families of Belgian, British and French descent. The human genome was screened with microsatellite markers spaced at 10-cM intervals and significant evidence for linkage to the disea se was observed on chromosome 8p21, with a maximum two-point lod score of 8 .26 for D8S1786 at a recombination fraction of 0. Recombinants narrowed the region of interest to a genetic interval of about 12 cM flanked by markers D8S280 and D8S1839. This interval contains the hairless gene which is muta ted in autosomal recessive congenital atrichia. Sequencing of the entire co ding region and intronic splice sites of the hairless gene in these three f amilies and in two unrelated familial cases revealed several polymorphic ch anges but failed to identify causative mutations. Nine other genes located within this region and expressed in skin were also excluded by mutation ana lysis. Together with a recent linkage study performed in a Dutch and a Brit ish family by van Steensel et al these results provide evidence for the pre sence of a gene distinct from hairless in chromosomal region 8p21 playing a n important role in hair follicle biology.