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. 2022 Apr;141(3-4):865-875.
doi: 10.1007/s00439-021-02351-7. Epub 2021 Sep 18.

Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan

Yoh-Ichiro Iwasa  1 , Shin-Ya Nishio  2 , Hidekane Yoshimura  1 , Akiko Sugaya  3 , Yuko Kataoka  3 , Yukihide Maeda  3 , Yukihiko Kanda  4 , Kyoko Nagai  5 , Yasushi Naito  6 , Hiroshi Yamazaki  6 , Tetsuo Ikezono  7 , Han Matsuda  7 , Masako Nakai  8 , Risa Tona  8 , Yuika Sakurai  9 , Remi Motegi  10 , Hidehiko Takeda  11 , Marina Kobayashi  11 , Chiharu Kihara  12 , Takashi Ishino  13 , Shin-Ya Morita  14 , Satoshi Iwasaki  15 , Masahiro Takahashi  15 , Sakiko Furutate  15 , Shin-Ichiro Oka  15 , Toshinori Kubota  16 , Yasuhiro Arai  17 , Yumiko Kobayashi  18 , Daisuke Kikuchi  19 , Tomoko Shintani  20 , Noriko Ogasawara  20 , Yohei Honkura  21 , Shuji Izumi  22 , Misako Hyogo  23 , Yuzuru Ninoyu  23 , Mayumi Suematsu  23 , Jun Nakayama  24 , Nana Tsuchihashi  25 , Mayuri Okami  26 , Hideaki Sakata  27 , Hiroshi Yoshihashi  28 , Taisuke Kobayashi  29 , Kozo Kumakawa  30 , Tadao Yoshida  31 , Tomoko Esaki  32 , Shin-Ichi Usami  33
Affiliations

Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan

Yoh-Ichiro Iwasa et al. Hum Genet. 2022 Apr.

Erratum in

  • Correction to: Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.
    Iwasa YI, Nishio SY, Yoshimura H, Sugaya A, Kataoka Y, Maeda Y, Kanda Y, Nagai K, Naito Y, Yamazaki H, Ikezono T, Matsuda H, Nakai M, Tona R, Sakurai Y, Motegi R, Takeda H, Kobayashi M, Kihara C, Ishino T, Morita SY, Iwasaki S, Takahashi M, Furutate S, Oka SI, Kubota T, Arai Y, Kobayashi Y, Kikuchi D, Shintani T, Ogasawara N, Honkura Y, Izumi S, Hyogo M, Ninoyu Y, Suematsu M, Nakayama J, Tsuchihashi N, Okami M, Sakata H, Yoshihashi H, Kobayashi T, Kumakawa K, Yoshida T, Esaki T, Usami SI. Iwasa YI, et al. Hum Genet. 2022 Apr;141(3-4):993-995. doi: 10.1007/s00439-021-02392-y. Hum Genet. 2022. PMID: 34727261 Free PMC article. No abstract available.

Abstract

Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

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Figures

Fig. 1
Fig. 1
Clinical characteristics of the OTOF-related hearing loss patients in this study. a Hearing level in PTA or COR in very young children. b Detection of hearing loss. c Intervention for hearing loss. NA not applicable, n number of patients
Fig. 2
Fig. 2
Detailed information of newborn hearing screening (NBHS). a Results of NBHS for all patients in this study. b, c Result of NBHS by each screening method (AABR and OAE)
Fig. 3
Fig. 3
Performance of cochlear implantation for OTOF-related hearing loss. a Hearing threshold with cochlear implants was available for 36 patients who had used CIs for more than 2 years. b The CAP scale was available for 33 patients
Fig. 4
Fig. 4
Detailed information on the disappearance of OAE response. a Timing of the disappearance of OAE response in the ear in which OAE response remained longer or the current status of OAE response. b Results at the last OAE testing
Fig. 5
Fig. 5
Summary of genotype–phenotype correlations in this and previous studies. a Mutation type and hearing severity in this and previous studies. b Hearing severity of patients with two truncating mutations. c Hearing severity of patients with truncating and non-truncating mutations (excluding p.Arg1939Gln). d Hearing severity of patients with two non-truncating mutations (excluding p.Arg1939Gln)
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