WFS1 mutations in hearing-impaired children

Abstract

Objective: Mutations in the WFS1 gene can cause Wolfram syndrome or nonsyndromic hearing impairment (HI). The objective of this study was to ascertain the presence of mutations in WFS1 among children with HI from unknown causes. Design: We screened 105 Finnish children with HI for mutations in exon 8 in WFS1. Study sample: Children were born in a defined area in Northern Finland and they had sensorineural, mild to profound, syndromic, or nonsyndromic HI. They were negative for GJB2 mutations and for the m.1555A> G and m.3243A> G mutations in mitochondrial DNA. Results: We found three rare variants and the novel p.Gly831Ser variant in WFS1. Segregation analysis suggested that the novel variant had arisen de novo. The p.Gly831Ser variant may be a new member to the group of heterozygous WFS1 mutations that lead to HI, while the pathogenicity of the rare variant p.Gly674Arg remained unclear. The other two rare variants, p.Glu385Lys and p.Glu776Val, did not segregate with HI in the families. Conclusions: WFS1 gene mutations are a rare cause of HI among Finnish children with HI.

Key Words::

• Wolframin
• DFNA6/14/38
• hereditary
• hearing loss
• deafness
• genetic

Acknowledgements

The authors are grateful to the families who participated in this study. The expert technical assistance of Ms. Anja Heikkinen and Ms. Pirjo Keränen is acknowledged. This work was supported in part by grants from the Academy of Finland (project number 127764), Oulu University Hospital, the Ear Research Foundation, the Arvo and Lea Ylppö Foundation, and the National Graduate School of Clinical Investigation.

Declaration of interest: The authors declare no conflict of interest.

Supplementary material available online at http://www.informahealthcare.com/doi/abs/10.3109/14992027.2014.887230

Supplementary Figure 1.