Hearing loss associated with enlarged vestibular aqueduct and Mondini dysplasia is caused by splice-site mutation in the PDS gene.

Recessive mutations of PDS gene are the common causes of Pendred syndrome and non-syndromic hearing loss associated with temporal bone abnormalities ranging from isolated enlargement of the vestibular aqueduct (EVA) to Mondini dysplasia. In this study we evaluate the relationship between EVA and Mondini dysplasia in 10 prelingual deaf patients and PDS gene mutation. One of three mutations, IVS7-2A-->G, IVS16-6G-->A or IVS15+5G-->A, was identified in the PDS gene in each patient. In family studies of four probands with the IVS7-2A-->G mutation, we found that this mutation was inherited from the same mutant alleles of parental origin. The effect of IVS7-2A-->G mutation on PDS gene expression was determined by reverse transcription and polymerase chain reaction (RT-PCR). Sequencing of the RT-PCR products revealed that the PDS transcripts from the allele with IVS7-2A-->G mutation lose the entire exon 8, resulting in a joining of exons 7 and 9. Deletion of the exon 8 results in frameshift and premature termination of translation. Haplotype analysis showed a significant haplotype shared among the family members carrying IVS7-2A-->G mutation, suggesting that they may be derived from a common ancestor. Our results provide evidence that hearing loss with EVA and Mondini dysplasia may be caused by splice-site mutation in the PDS gene.

Mutations of Cx26 gene (GJB2) for prelingual deafness in Taiwan.

Mutations in the Cx26 (GJB2) gene have been shown to be responsible for a major part of autosomal recessive non-syndromic inherited prelingual deafness. We have sequenced the coding region of GJB2 gene from 169 Taiwanese patients with prelingual deafness and 100 unrelated normal individuals. In the deaf patients, three mutations were found: two novel mutations, 551G-->A, and 299-300delAT, and one previously described mutation, 235delC. Four previously reported polymorphisms, 79G-->A, 109G-->A, 341A-->G, and 608T-->C, were also found in both deaf patients and normal individuals and one new possible polymorphism, 558G-->A, which was only found in a patient. Interestingly, we did not find the 35delG allele, which is commonly found in the Caucasian population, either in the patients or in normal individuals we examined. Our data also showed 235delC to be the most common type of mutation found in Cx26 mutants (approximately 57%). Therefore, based on our findings, we have developed a simple molecular test for the 235delC mutation and it should be of considerable help to those families to understand the cause of their children having the prelingual deafness.