Novel ATP6V1B1 mutations in distal renal tubular acidosis and hearing loss

Abstract

Conclusion: Novel ATP6V1B1 mutations were found in a patient with distal renal tubular acidosis (dRTA), hearing loss (HL), and enlargement of the vestibular aqueduct (EVA). The deterioration of HL and vertiginous attacks may be associated with the disruption of the endolymph pH homeostasis. Objectives: To study the audiovestibular functions and to identify the causative gene. Methods: This study enrolled a Japanese family, where the proband showed type 1 dRTA, early onset HL, and bilateral EVA. A deterioration of HL occurred several times in both ears. Vertiginous attacks were always associated with a deterioration of HL. Audiovestibular examinations included distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABRs), caloric testing, and vestibular evoked myogenic potentials (VEMPs). Direct sequencing was utilized to screen for ATP6V1B1, SLC26A4, and GJB2 mutations. Results: The findings of DPOAEs and ABRs indicated cochlear HL. The vestibular function was thought to be mildly impaired according to the caloric responses and VEMP findings. Two novel ATP6V1B1 mutations of a heterozygous 15 base-pair deletion (c.756_770del) in exon 7 and a heterozygous 1 base-pair insertion (c.1242_1243insC) in exon 12 were detected in a compound heterozygous state. No mutation was identified in either SLC26A4 or GJB2.

Keywords::

• Deafness
• vertigo
• vestibular evoked myogenic potentials
• enlargement of vestibular aqueduct
• large vestibular aqueduct

Acknowledgments

We thank all of the family members who participated in this study. The study was supported in part by Grants-in-Aid for Scientific Research (nos 19591960, 15790924, 14370539, 16659462, 16012215) from the Ministry of Health, Labour and Welfare of Japan, and by Health and Labour Sciences Research Grants (H13-006; Researches on Sensory and Communicative Disorders, and H14-21 and no. 17242101; Research on Measures for Intractable Diseases) from the Ministry of Health, Labour and Welfare of Japan.

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