Two novel mutations in ILDR1 gene cause autosomal recessive nonsyndromic hearing loss in consanguineous Iranian families

In a recent screening programme on hearing loss (HL), we examined 17 common autosomal recessive nonsyndromic hearing loss (ARNSHL) genes in every consanguineous Iranian family with ARNSHL that was referred to our centre. We first screened GJB2 mutations and then utilized a panel of three to four short tandem repeats to analyse rest of the loci. Once a homozygous by descent (HBD) pattern was observed for a given locus, direct sequencing was performed to identify the possible mutation. Families that did not show HBD pattern were screened through otologic sequence capture of pathogenic exons (OtoSCOPE) targeted sequencing panel (http://medicine.uiowa.edu/morl/otoscope/). Using this strategy, we identified two novel mutations in the immunoglobuline-like domain-containing receptor 1 gene (ILDR1, MIM 609739): a 2-bp deletion, c.1217-18delTC and a substitution, c.305T>A, in consanguineous Iranian deaf families. HL, which is the most common sensorineural impairment in humans, is caused by genetic defects in about half of all cases (Babanejad et al. 2012). In Iran, the frequency of HL is one in every 166 individuals and it ranks as the second most common disabling genetic impairment next to intellectual disability (Mahdieh et al. 2010; Babanejad et al. 2012). The ILDR1 gene in the DFNB42 locus (MIM 609646), which is located on chromosome 3q13.33, codes type-I transmembrane protein with a crucial role in epithelial barrier function in the ear (Borck et al. 2011; Higashi et al. 2013). Mutations in the ILDR1 gene are common in the Iranian deaf population and have been reported in five unrelated families (Borck et al. 2011; Babanejad et al. 2012; Diaz-Horta et al. 2012). Additionally, one deaf family from Saudi Arabia and nine from Pakistan were also identified with ILDR1 mutations (Aslam et al. 2005; Borck et al. 2011; Ramzan et al. 2014). In this study, we identified two other Iranian