Novel mutations in the pejvakin gene are associated with autosomal recessive non‐syndromic hearing loss in Iranian families

To the Editor: Hearing loss is a very heterogeneous disorder and may be due to genetic or environmental causes, or both. The incidence of pre-lingual deafness is about 1 in 1000 neonates of which more than 60% of cases are inherited (1–3). About 80% of hereditary deafness cases are nonsyndromic and the major mode of inheritance is autosomal recessive (4). A novel gene, DFNB59 encoding pejvakin located on chromosome 2q31.2, has been very recently shown to cause neural deafness in four Iranian families. The pejvakin gene is predicted to encode a polypeptide of 352 amino acids containing a nuclear localization signal in residues 249–258 and zincbinding motif in residues 305–331 (5). Here, we report mutation analysis for DFNB59 gene in 30 autosomal recessive non-syndromic hearing loss (ARNSHL) families, with an average of five deaf individuals in each family, which also originate from six provinces of Iran. Thirteen families from Chaharmahal va Bakhtiari (southwest), five families from Gilan (north), four families from Khoozestan (southwest), three families from Azerbaijan sharqi (northwest), three families from Kordestan (west) and two families from Tehran (central) were studied. All samples had been previously excluded for mutations in the GJB2 gene (6–11). All patients were clinically characterized and examined for puretone audiometry and were found to have mild to profound sensorineural hearing loss. Informed consent was obtained from all subjects or parents of underaged patients. The DFNB59 gene consists of seven exons, in which the first exon is non-coding. The entire coding region of the DFNB59 gene was polymerase chain reaction amplified and directly sequenced. The resultant sequences were compared with reference sequence NM_001042702 using SEQSCAPE V2.0 software. To date, only two pathogenic mutations (T54I and R183W) in four pedigrees of a cohort of Iranian consanguineous families have previously been reported (5) and the presence of DFNB59 sequence variations in other populations is not yet known. In the current study, five additional DFNB59 sequence variations were identified including two frameshift (c.726delT and c.988delG) and three missense (c.793C.T, c.793C.G and c.874G.A) changes (Table 1, Fig. 1d). Our data indicated that two novel variants (c.726delT and c.988delG), which are predicted to lead to premature termination at codons 248 and 336, respectively, co-segregate with the severe to profound disease phenotype (Fig. 1a–c) and are not found in 100 control