OTOF mutation screening in Japanese severe to profound recessive hearing loss patients.
BACKGROUND
Auditory neuropathy spectrum disorder (ANSD) is a unique form of hearing loss that involves absence or severe abnormality of auditory brainstem response (ABR), but also the presence of otoacoustic emissions (OAEs). However, with age, the OAEs disappear, making it difficult to distinguish this condition from other nonsyndromic hearing loss. Therefore, the frequency of ANSD may be underestimated. The aim of this study was to determine what portion of nonsyndromic hearing loss is caused by mutations of OTOF, the major responsible gene for nonsyndromic ANSD.


METHODS
We screened 160 unrelated Japanese with severe to profound recessive nonsyndromic hearing loss (ARNSHL) without GJB2 or SLC26A4 mutations, and 192 controls with normal hearing.


RESULTS
We identified five pathogenic OTOF mutations (p.D398E, p.Y474X, p.N727S, p.R1856Q and p.R1939Q) and six novel, possibly pathogenic variants (p.D450E, p.W717X, p.S1368X, p.R1583H, p.V1778I, and p.E1803A).


CONCLUSIONS
The present study showed that OTOF mutations accounted for 3.2-7.3% of severe to profound ARNSHL patients in Japan. OTOF mutations are thus a frequent cause in the Japanese deafness population and mutation screening should be considered regardless of the presence/absence of OAEs.
Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. usami@shinshu-u.ac.jp.
Yoh-ichiro
Y
Iwasa
Shin-ya
SY
Nishio
Hidekane
H
Yoshimura
Yukihiko
Y
Kanda
Kozo
K
Kumakawa
Satoko
S
Abe
Yasushi
Y
Naito
Kyoko
K
Nagai
Shin-ichi
S
Usami
D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D018389:Codon, Nonsense; D000072259:Connexin 26; D017630:Connexins; D005091:Exons; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007564:Japan; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary
D018389:Codon, Nonsense; D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; C118457:OTOF protein, human; D000072259:Connexin 26