Digenic inheritance of GJB4 gene in autosomal recessive Non-syndromic hearing loss patients with one mutant GJB2 allele.

Autosomal Recessive Non-syndromic Hearing Loss (ARNSHL)، in up to 50 percent of the cases، is caused by mutations in GJB2 (GJ: Gap Junction) gene، encoding connexin 26. However 10 to 42 percent of patients with recessive mutations are carriers of only one mutant GJB2 allele. Mutations in GJB4 gene encoding Cx30. 3 can also lead to hearing loss. Mixing of different connexins in heteromeric and heterotypic GJ assemblies is possible. The aim of this study is to answer whether variations GJB4 gene can be the second mutant allele causing the disease in Digenic mode of inheritance in the GJB2 heterozygous cases studied.

In this descriptive study 42 subjects with ARNSHL from seven provinces of Iran were examined and using polymerase chain reaction (PCR) then conservation of involved amino acids was obtained. According to the variations found in patients، 200 hearing control samples were tested sequenced using Restriction Fragment Length Polymorphism (PCR-RFLP) method.

In GJB4 gene five heterozygous variations (c. 451C>A، c. 219C>T، c. 507C>G، c. 155_158delTCTG، c. 542C>T) were found in five patients and 13 control individuals. c. 542C>T variation was not detected in control samples and conservation score of corresponding amino acid was very high. Conclution: Regarding the obtained evidences، it is suggested that c. 542C>T variation in GJB4 and other variations in this gene with lower possibility might contribute to ARNSHL in digenic pattern in heterozygote carriers of GJB2.