Abstract Background Variants of mitochondrial DNA (mtDNA) have been evaluated for their association with hearing loss. Although ethnic background affects the spectrum of mtDNA variants, systematic mutational analysis of mtDNA in Japanese patients with hearing loss has not been reported. Methods Using denaturing high-performance liquid chromatography combined with direct sequencing and cloning-sequencing, Japanese patients with prelingual (N = 54) or postlingual (N = 80) sensorineural hearing loss not having pathogenic mutations of m.1555A > G and m.3243A > G nor <it>GJB2 </it>were subjected to mutational analysis of mtDNA genes (<it>12S rRNA</it>, <it>tRNA</it><it>Leu(UUR)</it>, <it>tRNA</it><it>Ser(UCN)</it>, <it>tRNA</it><it>Lys</it>, <it>tRNA</it><it>His</it>, <it>tRNA</it><it>Ser(AGY)</it>, and <it>tRNA</it><it>Glu</it>). Results We discovered 15 variants in <it>12S rRNA </it>and one homoplasmic m.7501A > G variant in <it>tRNA</it><it>Ser(UCN)</it>; no variants were detected in the other genes. Two criteria, namely the low frequency in the controls and the high conservation among animals, selected the m.904C > T and the m.1105T > C variants in <it>12S rRNA </it>as candidate pathogenic mutations. Alterations in the secondary structures of the two variant transcripts as well as that of m.7501A > G in <it>tRNA</it><it>Ser(UCN) </it>were predicted. Conclusions The m.904C > T variant was found to be a new candidate mutation associated with hearing loss. The m.1105T > C variant is unlikely to be pathogenic. The pathogenicity of the homoplasmic m.7501T > A variant awaits further study.</p

A Achilli

A Konings

A Kral

A Maasz

A Tessa

A Torroni

BJ van Den Bosch

C Bacino

C Herrnstadt

CC Morton

CM Sue

D Thyagarajan

Eiko Teruya

FJ del Castillo

FM Reid

H Kokotas

H Zhao

Hideki Mutai

Hidenobu Taiji

Hiroki Kakishima

Hiroko Kouike

Ikuko Takahashi-Kodomari

J Chen

J Lu

JA Maassen

JM van den Ouweland

K Kobayashi

K Sato

K Takahashi

K Verhoeven

L Jin

L Zhao

M Deschauer

M Hamada

M Laloi-Michelin

M Leveque

M Mancuso

M Mollers

M Rydzanicz

M Tanaka

MR Chaig

PF Chinnery

Q Wang

QP Kong

RM Andrews

S Anderson

S Usami

Shin-ichi Usami

T Matsunaga

T Oshima

Tatsuo Matsunaga

Torayuki Okuyama

TP Hutchin

V Tiranti

WY Young

X Tang

Y Goto

Y He

Y Kobayashi

Y Sakihara

Y Wada

YG Yao

Z Li

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