A novel 4-bp insertion mutation in EDA1 gene in a Pakistani family with X-linked hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by the absence or hypoplasia of hair, teeth, and eccrine sweat glands. The inheritance pattern of HED may be X-linked or autosomal (dominant or recessive). Mutations in the EDA 1 gene cause X-linked HED and mutations in either EDAR or EDARADD genes cause autosomal forms of HED. To search for a mutation in human EDA1 gene in a large Pakistani family demonstrating X-linked form of HED (XLHED), eight exons and splice junction sites of EDA1 gene were amplified by PCR from genomic DNA and sequenced directly in an ABI Prism 310 automated DNA sequencer. A novel four bases insertion mutation (913_914insTATA) was identified in exon 8 of the EDA 1 gene. This insertion introduces a reading frameshift leading to downstream premature termination codon in the same exon. In the present study a novel insertion mutation in EDA1 gene in a Pakistani family with XLHED has been reported. This extends our knowledge of mutations in EDA1 gene that define the pathogenic basis of HED.