Novel ATP6V1B1 mutations in distal renal tubular acidosis and hearing loss.
CONCLUSIONS
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.


OBJECTIVE
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.
Yashima
Takatoshi
T
Department of Otolaryngology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo113-8519, Japan.
Noguchi
Yoshihiro
Y
Kawashima
Yoshiyuki
Y
Rai
Tatemitsu
T
Ito
Taku
T
Kitamura
Ken
K
D000141:Acidosis, Renal Tubular / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D044466:Asian People; D002648:Child; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis; D034381:Hearing Loss / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*; D014717:Vertigo / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D014723:Vestibular Aqueduct / Q000002:abnormalities; D058585:Vestibular Evoked Myogenic Potentials
C509766:ATP6V1B1 protein, human; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D025262:Vacuolar Proton-Translocating ATPases