Background: Hypohidrotic ectodermal dysplasia (HED) is a human heritable disorder characterized by sparse hair, a lack of sweat glands and malformation of teeth. There are X-linked, autosomal recessive and autosomal dominant forms of this disorder. Mutations in the EDA gene cause X-linked HED and mutations in either the EDAR or the EDARADD genes cause autosomal forms of HED.
Objectives: To identify pathogenic mutations in two consanguineous Pakistani families (A and B) with 11 affected individuals demonstrating the autosomal recessive form of HED.
Methods: Genotyping of 17 members of the two families, including eight affected and nine unaffected individuals, was carried out by using polymorphic markers D2S293, D2S1893 and D2S1891, which are closely linked to the EDAR gene on chromosome 2q11-q13. To screen for mutations in the EDAR gene, all of its exons and splice junctions were polymerase chain reaction amplified from genomic DNA and sequenced directly in an ABI Prism 310 automated sequencer.
Results: Genotyping results showed linkage in both the Pakistani families to the EDAR locus. Sequence analysis of the EDAR gene identified two novel mutations in the families: a missense mutation (G382S) in family A and a 4-bp deletion (718delAAAG) in family B.
Conclusions: We describe novel mutations in the EDAR gene in two Pakistani families affected with the autosomal recessive form of HED. Our findings extend the body of evidence that supports the importance of the ectodysplasin A1 isoform receptor, a member of the tumour necrosis factor receptor family, in the development of ectodermal appendages.