024 Atrichia with Papular Lesions Resulting from Compound Heterozygous Mutations in the Hairless Gene: A Lesson for Differential Diagnosis of Alopecia Universalis.

Wolfram Henn1, Abraham Zlotogorski3, Andrei A. Panteleyev, Hansotto Zaun2, and Angela M. Christiano. 1Institute of Human Genetics, and 2Dept. of Dermatology, Saarland University, Homburg/Saar, Germany; 3Hadassah Medical Center, Jerusalem, Israel; Departments of Dermatology and Genetics & Development, Columbia University, New York, NY Atrichia with papular lesions (APL) is a rare, autosomal recessive form of total alopecia, in which mutations in the hairless (hr) gene have been shown to underlie the phenotype. We suspect that APL is actually much more common that previous population estimates suggest, because we believe the disorder is frequently misdiagnosed as alopecia universalis. To date, mutations identified in the hairless gene have all been homozygous mutations in probands within families with extensive consanguinity, where identity-bydescent (IBD) was anticipated. We sought to investigate whether APL might also be found among patients in small families without obvious IBD, particularly those giving a history of 1) normal hair at birth that was shed and never regrew; and 2) ‘alopecia universalis’ that is recalcitrant to any treatment. In this study, we identified a small family of German origin in which two of four siblings were affected and gave this clinical history. Direct sequence analysis of the hr gene in one proband revealed distinct mutations on each allele. The first was a 2 bp deletion of the splice acceptor site of intron 13 (2847-2delAG), and the second was a nonsense mutation in exon 19 (Q1176X). This is the first demonstration of compound heterozygous mutations in the hr gene. These findings support the hypothesis that APL can exist in small families without IBD, and underscore the possibility that APL may be masquerading clinically as alopecia universalis. We anticipate that an increased recognition of this disorder will result in accurate discrimination between APL and alopecia universalis, thus sparing unnecessary treatment to affected patients.