Copyright © 1999 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 64, Issue 5, 1323-1329, 1 May 1999
doi:10.1086/302368
Identification of a Genetic Defect in the Hairless Gene in Atrichia with Papular Lesions: Evidence for Phenotypic Heterogeneity among Inherited Atrichias
Eli Sprecher1, 2, Reuven Bergman1, Raymonde Szargel2, Rachel Friedman-Birnbaum1 and Nadine Cohen2, 
, 
1 Department of Dermatology, Rambam Medical Center, Technion-Israel Institute of Technology, Bruce Rappaport Faculty of Medicine, Haifa, Israel
2 Department of Genetics,Tamkin Human Molecular Genetics Research Facility, Technion-Israel Institute of Technology, Bruce Rappaport Faculty of Medicine, Haifa, Israel
Address for correspondence and reprints: Dr. Nadine Cohen, Department of Genetics, Tamkin Human Molecular Genetics Research Facility, Technion-Israel Institute of Technology, Bruce Rappaport Faculty of Medicine, POB 9649, Haifa 31096, IsraelAbstract
Recently, we showed that atrichia with papular lesions (APL), a rare inherited form of alopecia, is transmitted as an autosomal recessive trait in a large inbred kindred of Israeli-Arab origin. Furthermore, we mapped the APL locus to a 5-cM region of chromosome 8p12 in this family. The human “hairless” gene is a candidate target gene for the disease mutation because it maps to the APL locus and because it was recently found to be mutated in a related but clinically distinct form of alopecia known as “alopecia universalis” or “congenital alopecia.” In the present study, the coding sequence of the hairless gene was compared by reverse transcription–PCR in fibroblast cell lines derived from an affected patient and an unrelated individual. We identified a single-base deletion (3434delC) in the hairless gene that cosegregated with the disease phenotype in the family. This deletion is predicted to cause a frameshift mutation in the highly conserved C-terminal part of the hairless protein, a region putatively involved in the transcription factor activity of the hairless gene product. The present results are indicative of phenotypic heterogeneity in inherited atrichias caused by mutations in the hairless gene, suggesting different roles for the regions mutated in APL and in other forms of congenital atrichia during hair development.
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