Penetrance of novel mutations of endothelin-B receptor gene in Pakistani families with Waardenburg syndrome

Mutations in endothelin-ß-receptor gene (ednrb) gene have been reported to cause waardenburg syndrome (ws4) in humans. we investigated novel mutations in ednrb gene and their association with ws4 in two pakistani families named wspk1 and wspk2 using pcr and direct sequencing technique. a transition of t to c in codon (l361s) in exon 5 of ednrb gene was found in family wspk1. the mutation was found in the homozygote patients with ws4 and their asymptomatic heterozygote parents. in second family wspk2,three mutations; a g to c transversion in codon 335 (c335s) in exon 5,a transition of t to c in codon (l361s) in exon 5 and a non coding transversion of t to a at - 30 nucleotide position of exon 5 were identified in the homozyote patients and the heterozygote asymptomatic parents. the patients and asymptomatic parents carried the same mutations. in both families,the parents have consanguineous marriage. in this study,we have identified the penetrance of the novel mutations of ednrb gene in two pakistani families suffering with ws4. this is first report of ws4 and its correlation with the novel mutation described herein. copyright 2012 zoological society of pakistan.