F18 A NONSENSE MUTATION IN THE CORNEODESMOSIN GENE IN A MEXICAN FAMILY WITH HYPOTRICHOSIS SIMPLEX OF THE SCALP
Dávalos NO1, García-Vargas A2, Pforr J3, Dávalos IP4, Picos-Cárdenas VJ 4, García-Cruz D4, Figuera LE4, Kruse R5, Nöthen MM6, Betz RC3
1Instituto de Genética Humana "Dr. Enrique Corona Rivera" CUCS, Universidad de Guadalajara, Mexico
2Instituto Dermatológico de Jalisco "Dr. José Barba Rubio" SSJ, Guadalajara, Mexico
3Institute of Human Genetics, University of Bonn, Germany
4División de Genética, CIBO-IMSS, Guadalajara, Mexico
5Department of Dermatology, University of Düsseldorf, Germany
6Life & Brain Center, University of Bonn, Germany

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. Here, we describe a Mexican family presenting HSS. The pedigree extends over six generations comprising 156 individuals, 42 of whom are affected. By direct sequencing of the two exons of the CDSN gene, a novel nonsense mutation was identified in the index patient in exon 2, resulting in a premature stop codon (Y239 X). The mutation co-segregated in the family (17 family members, 9 of whom were affected) and was not found in 300 control chromosomes using a restriction enzyme analysis with PsuI. 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 for HSS are clustered in a region including 40 amino acids of exon 2 in the CDSN gene which is in accordance with a dominant negative effect conferred by aggregates of truncated CDSN proteins.