High frequency of<i>OTOF</i>mutations in Chinese infants with congenital auditory neuropathy spectrum disorder

Zhang, Q.-J.; Han, Bing; Liang, Liuqin; Zong, Lei; Shi, Wei; Wang, H.-Y.; Xie, Linyi; Zhao, Cui; Zhang, C.; Yin, Zifang; Wang, D.-Y.; Petit, Christine; Guan, Jing; Wang, Q.-J.

doi:10.1111/cge.12744

Cited by 32 publications

(24 citation statements)

References 25 publications

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“…More patients may be discovered as the use of genetic testing in the diagnosis of auditory neuropathy becomes more widespread [ 4 – 8 ]; however, no prevalence studies have been performed to date. In our previous study, we confirmed that OTOF is the most common gene-causing congenital auditory neuropathy [ 42 ]. In contrast, for patients with late-onset AN, the etiology varies and is associated with optic atrophy, sensorimotor neuropathy, and other peripheral neuropathies.…”

Section: Discussionsupporting

confidence: 72%

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

Wang

Dai

et al. 2020

Neural Plasticity

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To decipher the genotype-phenotype correlation of auditory neuropathy (AN) caused by AIFM1 variations, as well as the phenotype progression of these patients, exploring the potential molecular pathogenic mechanism of AN. A total of 36 families of individuals with AN (50 cases) with AIFM1 variations were recruited and identified by Sanger sequencing or next-generation sequencing; the participants included 30 patients from 16 reported families and 20 new cases. We found that AIFM1-positive cases accounted for 18.6% of late-onset AN cases. Of the 50 AN patients with AIFM1 variants, 45 were male and 5 were female. The hotspot variation of this gene was p.Leu344Phe, accounting for 36.1%. A total of 19 AIFM1 variants were reported in this study, including 7 novel ones. A follow-up study was performed on 30 previously reported AIFM1-positive subjects, 16 follow-up cases (53.3%) were included in this study, and follow-up periods were recorded from 1 to 23 years with average 9.75±9.89 years. There was no hearing threshold increase during the short-term follow-up period (1-10 years), but the low-frequency and high-frequency hearing thresholds showed a significant increase with the prolongation of follow-up time. The speech discrimination score progressed gradually and significantly along with the course of the disease and showed a more serious decline, which was disproportionately worse than the pure tone threshold. In addition to the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is also observed in AIFM1-related AN and affects females. In conclusion, we confirmed that AIFM1 is the primary related gene among late-onset AN cases, and the most common recurrent variant is p.Leu344Phe. Except for the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is another probability of AIFM1-related AN, with females affected. Phenotypical features of AIFM1-related AN suggested that auditory dyssynchrony progressively worsened over time.

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Section: Discussionsupporting

confidence: 72%

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

Wang

Dai

et al. 2020

Neural Plasticity

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“…Among nonsyndromic ANSD patients, OTOF mutations account for 18% in Chinese [5], 57% in Japanese [6], 20% in Korean [7], 27% in Brazilian [8], and 87% in Spanish [9]. Further, according to Zhang et al, more than 41% of congenital ANSD cases in China are caused mainly by OTOF mutations [10]. To date, over 110 mutations in the OTOF gene have been recorded in the Human Gene Mutation Database (HGMD) (http://www.hgmd.cf.ac.uk/ac/index.php).…”

Section: Introductionmentioning

confidence: 99%

Auditory Neuropathy Spectrum Disorder due to Two Novel Compound Heterozygous OTOF Mutations in Two Chinese Families

et al. 2019

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Auditory neuropathy spectrum disorder (ANSD), also called auditory neuropathy (AN), is a unique type of prelingual hearing impairment. Up to 10% of deaf infants and children are affected by this disease. Mutation of the OTOF gene which encodes otoferlin is the common cause of congenital nonsyndromic ANSD. To date, over 110 mutations have been identified in the OTOF gene according to the Human Gene Mutation Database (HGMD). Here, next-generation sequencing (NGS) revealed that the compound heterozygous mutations c.4748G>A/c.2523+1G>T and c.5248G>C/c.5098G>C of the OTOF gene were present in two Chinese ANSD patients. Each patient had a known pathogenic mutation (c.4748G>A or c.5098G>C) and a novel mutation (c.2523+1G>T or c.5248G>C). Comparative amino acid sequence analysis across different species revealed that the residues at these novel mutation sites are evolutionarily highly conservative. This indicated that the novel mutations were possible causes of the disorder in the patients. Our findings extend the OTOF mutation spectrum and further confirm the role of the OTOF gene in ANSD.

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“…Both genetic and environmental factors cause ANSD, such as hyperbilirubinemia, thiamine deficiency, hypoxia, and noise-induced and age-related hearing loss (Shearer 2019). OTOFrelated ANSD is the most prevalent form of ANSD, and it is reported that 23-90.9% of pediatric cases of ANSD are caused by OTOF mutations (Rodríguez-Ballesteros et al 2008;Matsunaga et al 2012;Zhang et al 2016;Kim et al 2018). OTOF is mainly expressed in the inner hair cells (IHCs), and mutations in the OTOF gene cause dysfunction of synaptic exocytosis at the ribbon synapse (Roux et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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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High frequency ofOTOFmutations in Chinese infants with congenital auditory neuropathy spectrum disorder

Cited by 32 publications

References 25 publications

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

Auditory Neuropathy Spectrum Disorder due to Two Novel Compound Heterozygous OTOF Mutations in Two Chinese Families

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

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