Novel mutations of SLC26A4 in Chinese patients with nonsyndromic hearing loss

Abstract

Conclusions: This study demonstrated high prevalence of GJB2, SLC26A4, and mtDNA A1555G mutations in Chinese patients with nonsyndromic hearing loss and discovered eight novel mutations in SLC26A4. Most of these novel mutations were predicted pathogenic variants. Objectives: Nonsyndromic hearing loss is the most common neurosensory deafness where the majority of patients have highly diversified genetic defects. This study aimed to define the genetic profile of deafness in a Chinese population with potential to discover novel mutations. Methods: A total of 227 segregating deaf students and 200 individuals with normal hearing were enrolled. With the Sanger sequencing chemistry, direct sequencing was performed on entire coding regions of GJB2, GJB3, SLC26A4, and mtDNA m.C1494T and m.A1555G. Results: Direct sequencing analysis revealed that 53 (23.35%) of 227 patients carried at least 1 mutant allele in GJB2, 40 (17.62%) patients in SLC26A4, 5 (2.20%) patients in mtDNA A1555G, and 1 (0.44%) patient in mtDNA C1494T mutations. Four patients carried three unclassified mutations in GJB3 genes. Overall 38 mutant variants were detected in this cohort of patients, including 8 novel mutations in SLC26A4. The eight novel variants were six missense substitutions (p.V163L, p.G222S, p.A456D, p.N457I, p.C466Y, p.F667L), one nonsense mutation (p.W472X), and one frameshift (p.Asn612Ilefs×23).

Keywords::

• Sanger sequencing
• pathogenic
• heterogeneity
• compound heterozygote

Acknowledgments

The authors would like to thank the patients who participated in this study and the research teams of the Birth Defect Research Center & Pathology Research Center, Fudan University, Shanghai, China, who assisted with this research. This work was supported by the National Basic Research Program of China (973 program, no. 2011CB504502), the Key Program of Handan (1113108017), the Science and Technology Commission of Shanghai Major Basic Research Projects (09DJ1400602), Foundation of Ministry of Health no. 201202005, and the Research Special Fund of the Ministry of Health Public Service Sectors Funded Projects. The authors also would like to thank Handan Municipal Special Education School and Xingtai Municipal Special Education School (Hebei Province) for their fundamental support and contributions to this work.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.