title: Splice site mutations in the P-cadherin gene underlie hypotrichosis with juvenile macular dystrophy.
abstract: BACKGROUND
  Hypotrichosis with juvenile macular dystrophy (HJMD; OMIM 601553) is a rare autosomal recessive disorder characterized by hypotrichosis with short scalp hair and progressive macular dystrophy leading to blindness between the second and the fourth decades of life. HJMD is caused by mutations in the P-cadherin gene (CDH3), a member of the family of classical cadherins.
  
  
  METHODS
  We analyzed the DNA from members of 2 consanguineous Pakistani families with HJMD for mutations in the P-cadherin gene through direct sequencing.
  
  
  RESULTS
  We identified 2 splice site mutations in the P-cadherin gene in these families. One was a novel mutation, Ivs12-2A-->G and the other a recurrent mutation, Ivs10-1G-->T. A screening assay for the novel mutation ruled out the possibility of a polymorphism. Using haplotype analysis, we determined that the mutation, Ivs10-1G-->T, is a founder mutation in the Pakistani population.
  
  
  CONCLUSIONS
  We identified 2 splice site mutations in the CDH3 gene leading to HJMD, further enriching our understanding of HJMD versus ectodermal dysplasia, ectrodactyly and macular dystrophy syndrome.
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimomura
authors.forename: M
authors.initials: M
authors.lastname: Wajid
authors.forename: M
authors.initials: M
authors.lastname: Kurban
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000328:Adult; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D002648:Child; D003241:Consanguinity; D006239:Haplotypes; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D022821:RNA Splice Sites / Q000235:genetics*
chemical_list: D015820:Cadherins; D022821:RNA Splice Sites