Intragenic deletion mutation in the gene desmoglein 4 underlies autosomal recessive hypotrichosis in six consanguineous families

Abstract

Objectives Localized autosomal recessive hypotrichosis is a non-syndromic human hair loss disorder, affecting scalp, eyebrows and eyelashes, and other parts of the body. Six consanguineous families with this form of hair loss disorder were investigated at both the clinical and molecular levels. Methods Linkage in six families with twenty-one affected members was tested by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci including localized autosomal recessive hypotrichosis (LAH) 1, 2 and 3. Sequence analysis of the entire coding and splice sites of the gene DSG4 was performed to search for the disease-causing mutation. Results Genotyping established linkage in families to the DSG4 gene at LAH1 locus on chromosome 18q21.1. Sequence analysis detected an intragenic deletion mutation (Ex5-8 del) in affected members of all six families. Conclusion Identification of recurrent mutation in six additional Pakistani families strengthens the body of evidence that this is an ancestral mutation that is widespread among different Pakistani ethnic groups.