Abstract
Conclusions: There could be another candidate gene in DFNA2, which could be responsible for the hearing loss phenotype. Objective: We collected a four-generation family from the southern part of China with autosomal dominant sensorineural hearing impairment. In order to identify the responsible pathogenic mutations in this family, we set out to identify the locus and to sequentially analyze the candidate genes in the identified region. Methods: After family ascertainment and clinical analysis, exclusive analysis was performed. Then a genome-wide scan was performed using an Illumina Linkage-12 DNA Analysis Kit (average spacing 0.58 cM). Fine-mapping markers were genotyped to identify the locus. Finally, we performed haplotype analyses and candidate gene DNA sequencing for the family. Results: The known genetic loci and genes were not associated with our family. The genome-wide scan and haplotype analyses traced the disease to chromosome 1p34.2–p34.3 with maximum multi-point LOD score of 3.2, which overlaps with DFNA2. We failed to identify any of the known or novel variants within KCNQ4, a voltage-gated potassium channel gene, and GJB3, a gene that encodes the gap junction protein connexin 31, which were the cloned deafness genes in DFNA2.
Acknowledgments
This work was funded by the Chinese National Programs for High Technology Research and Development; contract grant no. NO.2007AA02Z445; National Nature Science Foundation of China, contract grant nos NO.30671150 and NO.30971589; general project of Hunan Science and Technology Agency, contract grant no. [2009] 42, Key Clinical Program of the Ministry of Health (2010–2012). We thank the patients and families for their collaboration in this project. We are grateful to Dr Danling Wang for helpful editing of the manuscript.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.