The gene for hypotrichosis of Marie Unna maps between D8S258 and D8S298: Exclusion of the hr gene by cDNA and genomic sequencing

Hypotrichosis of Marie Unna (MU) is an autosomal dominant hair-loss disorde r with onset in childhood. A genomewide search for the gene was performed i n a large Dutch family using 400 fluorescent microsatellite markers. Linkag e was detected with marker D8S258, and analysis of this family and a furthe r British kindred with additional markers in the region gave a combined max imum two-point LOD score of 13.42, with D8S560. Informative recombinants pl aced the MU gene in a 2.4-cM interval between markers D8S258 and D8S298. Re cently, recessive mutations in the hv gene were reported in families with c ongenital atrichia, and this gene was previously mapped close to the MU int erval. By radiation-hybrid mapping, we placed the hr gene close to D8S298 b ut were unable to exclude it from the MU interval. This, with the existence of the semidominant murine hr allele, prompted us to perform mutation anal ysis for this gene. Full-length sequencing of hr cDNA obtained from an affe cted individual showed no mutations. Similarly, screening of all exons of t he hr gene amplified from the genomic DNA of an affected individual reveale d no mutations. Analysis of expressed sequences and positional cloning of t he MU locus is underway.