A novel splice-site mutation in the CDH3 gene in hypotrichosis with juvenile macular dystrophy

Abstract

Background. Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse hair on the scalp and early blindness. Mutations in the CDH3 gene have been reported to underlie HJMD. Aim. To identify a gene responsible for HJMD in a large, four-generation Pakistani family. Methods. Genotyping of 13 members of the family, including 6 affected and 7 unaffected members, was carried out using polymorphic microsatellite markers closely linked to the CDH3 on chromosome 16q22.1. To screen for mutations in the CDH3 gene, all of its exons and splice junctions were amplified using PCR from genomic DNA and sequenced directly, using an automated DNA sequencer. Results. Microsatellite analysis showed linkage of the family to the CDH3 gene on chromosome 16q22.1. Sequence analysis of the CDH3 gene revealed a novel splice-site mutation (IVS10-1 G→T), leading to probable skipping of exon 11 and a shift in the reading frame. Conclusion. The mutation identified here represents the first mutation in the CDH3 gene causing HJMD in a Pakistani population. © 2008 The Author(s).