title: A non-sense mutation in the corneodesmosin gene in a Mexican family with hypotrichosis simplex of the scalp.
abstract: BACKGROUND
  Hypotrichosis simplex of the scalp (HSS; MIM 146520) is a rare autosomal dominant form of non-syndromic alopecia that affects men and women equally. Up to now, only a small number of families with HSS have been reported. The affected individuals experience a diffuse progressing hair loss from childhood to adulthood that is confined to the scalp. Recently, HSS has been mapped to the short arm of chromosome 6 (6p21.3), allowing mutations in the corneodesmosin gene (CDSN) to be identified as the cause of the disorder. To date, two stop mutations have been found in three unrelated families with HSS of different ethnic origin.
  
  
  OBJECTIVE
  To describe the first HSS-family with Latin American (Mexican) background comprising 6 generations and to identify a mutation in the CDSN gene.
  
  
  METHODS
  The patients were examined by a clinician and blood samples were taken. After DNA extraction, sequencing analysis of the CDSN gene and restriction enzyme analysis with PsuI were performed.
  
  
  RESULTS
  By direct sequencing of the two exons of the CDSN gene, a nonsense mutation was identified in the index patient in exon 2, resulting in a premature stop codon (Y239X). The mutation co-segregates perfectly in the family with the disease and was not found in 300 control chromosomes using a restriction enzyme analysis with PsuI.
  
  
  CONCLUSIONS
  A nonsense mutation was identified in the first family with HSS of Latin American ethnical background. Our data provide molecular genetic evidence for a 3rd stop mutation in exon 2 of the CDSN gene being responsible for HSS. All to date known nonsense mutations responsible 3 for HSS are clustered in a region of 40 amino acids which is in accordance with a dominant negative effect conferred by aggregates of truncated CDSN proteins.
authors.affiliation: Instituto de Genética Humana Dr. Enrique Corona Rivera, CUCS, Universidad de Guadalajara, Guadalajara, Mexico.
authors.forename: N O
authors.initials: NO
authors.lastname: Dávalos
authors.forename: A
authors.initials: A
authors.lastname: García-Vargas
authors.forename: J
authors.initials: J
authors.lastname: Pforr
authors.forename: I P
authors.initials: IP
authors.lastname: Dávalos
authors.forename: V J
authors.initials: VJ
authors.lastname: Picos-Cárdenas
authors.forename: D
authors.initials: D
authors.lastname: García-Cruz
authors.forename: R
authors.initials: R
authors.lastname: Kruse
authors.forename: L E
authors.initials: LE
authors.lastname: Figuera
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: R C
authors.initials: RC
authors.lastname: Betz
mesh_terms: D000293:Adolescent; D000505:Alopecia / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D018389:Codon, Nonsense; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008800:Mexico / Q000208:ethnology; D008875:Middle Aged; D010375:Pedigree
chemical_list: C109656:CDSN protein, human; D018389:Codon, Nonsense; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins