title: Mutations in the hairless gene underlie APL in three families of Pakistani origin.
abstract: BACKGROUND
  Atrichia with papular lesions (APL) (OMIM#209500) is a rare autosomal recessively inherited form of irreversible alopecia characterized by papular lesions of keratin-filled cysts on various regions of the body. Males and females are equally affected and present with a distinct pattern of total hair loss on scalp, axilla and body. It begins shortly after birth with the development of hair loss, and patients are normally devoid of eyelashes and eyebrows. Mutations in the hairless (HR) gene have been previously shown to be responsible for APL.
  
  
  OBJECTIVE
  In this study, we studied the molecular basis of APL in three unrelated families of Pakistani origin.
  
  
  METHODS
  Molecular analysis of the HR genes was performed on genomic DNA from probands and family members.
  
  
  RESULTS
  DNA sequencing of the HR gene in family A revealed a novel homozygous 2bp deletion in exon 6 leading to a frameshift and a downstream premature termination codon in exon 8 (1782-83delAG). In family B, we identified a novel homozygous deletion of a G nucleotide at the exon 15-intron 15 boundary, termed 3097delG. Family C carries a previously reported missense mutation consisting of an A-to-G transition at nucleotide 276 resulting in the mutation N970S in exon 14.
  
  
  CONCLUSIONS
  Two mutations identified in this study are novel mutations in the HR gene and extend the body of evidence implicating the hairless gene family in the pathogenesis of human skin disorders. The one previously reported mutation suggests it may represent a recurrent mutation, or alternatively, an allele that is widely dispersed around the world.
authors.affiliation: Department of Dermatology, Columbia University, College of Physicians & Surgeons, 630 West 168th Street VC15 204A, New York, NY 10032, USA.
authors.forename: Liv
authors.initials: L
authors.lastname: Kraemer
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wajid
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000505:Alopecia / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C490267:HR protein, human; D014157:Transcription Factors