Identification of both MT-RNR1 m.1555A>G and bi-allelic GJB2 mutations in probands with non-syndromic hearing loss

ObjectivesMutations in GJB2 and MT-RNR1 are common causes for non-syndromic sensorineural hearing loss (NSHL). In this study, we investigated the co-existence of both MT-RNR1 and bi-allelic GJB2 mutations in a large number of simplex and multiplex probands with NSHL.Methods485 simplex and 134 multiplex probands with NSHL were recruited for mutation screening of GJB2 and MT-RNR1 by bidirectional sequencing. Clinical features of probands with both MT-RNR1 and bi-allelic GJB2 mutations were further analyzed in comparison with extended family members.ResultsMT-RNR1m.1555A>G and bi-allelic GJB2 mutations were both detected in one (0.21%) simplex probands and two (1.49%) multiplex probands. Variable hearing phenotypes were found in a pair of siblings with both MT-RNR1 and bi-allelic GJB2 mutations.ConclusionMT-RNR1 and bi-allelic GJB2 mutations may co-exist not only in multiplex probands but also in simplex probands. The variable hearing phenotypes in closely-related family members may reflect the co-existence of different molecular causes and prompt extended genetic tests.