Abstract
Waardenburg syndrome (WS) is a neurocristopathy with an autosomal dominant mode of inheritance, and considerable clinical and genetic heterogeneity. WS type II is the most common type of WS in many populations presenting with sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eye, and pigmentary abnormalities of the hair and skin. To date, mutations of MITF, SOX10, and SNAI2 have been implicated in the pathogenesis of WS2. Although different pathogenic mutations have been reported in many ethnic groups, the data on Iranian WS2 patients is insufficient. 31 WS2 patients, including 22 men and 9 women from 14 families were included. Waardenburg consortium guidelines were employed for WS2 diagnosis. WS2 patients underwent screening for MITF, SOX10, and SNAI2 mutations using direct sequencing and MLPA analysis. Clinical evaluation revealed prominent phenotypic variability in Iranian WS2 patients. Sensorineural hearing impairment and heterochromia iridis were the most common features (67% and 45%, respectively), whereas anosmia was the least frequent phenotype. Molecular analysis revealed a de novo heterozygous c.640C>T (p.R214X) in MITF and a de novo heterozygous SOX10 gross deletion in the study population. Our data help illuminate the phenotypic and genotypic spectrum of WS2 in an Iranian series of patients, and could have implications for the genetic counseling of WS in Iran.