First report of prevalence c.IVS1+1G>A and del (GJB6-13S1854) mutations in Syrian families with non-syndromic sensorineural hearing loss

Abstract Objective Mutations in GJB2 and GJB6 genes are a frequent cause of congenital non-syndromic hearing loss ( NSHL ). Mutational screening has usually focused on coding region of GJB2 gene. A few studies have been conducted on the non-coding region and exon 1. c.IVS1+1G>A (a splice site mutation in GJB2 gene have been detected as disruptive mutation. Del ( GJB6 D13S1830) is found in many populations, but del ( GJB6 D13S1854 ) is reported from a few restricted countries. This study was carried out to investigate the prevalence of splice site mutation c.IVS1+1G>A and two common deletions in GJB6 gene as the genetic etiology of hearing impairment in 70 Syrian families. Methods The frequency of the c.IVS1+1G>A mutation and two deletions were determined by PCR-RFLP and A multiplex PCR assay. Result Our results showed a high prevalence of IVS1+1G > A mutation (20%) and del (GJB6-D13S1854) (15.7%) in deaf families. The homozygous genotype ( c.IVS1+1G>A / c.IVS1+1G>A ) was observed in one family and the compound heterozygous genotypes (c.35delG/ c.IVS1+1G>A ) and ( c.IVS1+1G>A/V153I ) were observed in 7 families and one family respectively. Also, the heterozygous state ( c.IVS1+1G>A /unknown) was detected in 5 families. The study of del( (GJB6-D13S1854) was showed a compound heterozygous genotype del( (GJB6-D13S1854)/c.IVS1+1G>A) in the same families (5 families) having heterozygous genotype of c.IVS1+1G>A mutation. Also, del (GJB6-D13S1854) is combined with c.35delG mutation in 2 families and it was observed in the heterozygous state del( GJB6-D13S1854 )/unknown) in 4 families. In contrast, the del (GJB6-D13S1830) described in many population was absent in our patients. Conclusion Our findings indicate to significant contribution of the splice site mutation and del (GJB6-D13S1854) in our deaf families and these mutations were important causes of hearing impairment.