Screening of OTOF mutations in Iran: A novel mutation and review

Mahdieh, Nejat; Shirkavand, Atefeh; Rabbani, Bahareh; Tekin, Mustafa; Akbari, Bahman; Akbari, Mohammad Taghi; Zeinali, Sirous

doi:10.1016/j.ijporl.2012.07.030

Cited by 32 publications

(27 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The currently-known spectrum of sequence variants of the OTOF gene includes more than 90 pathogenic mutations and over 50 neutral variants (Mahdieh et al, 2012;Rodríguez-Ballesteros et al, 2008). Pathogenic variants are responsible for the DFNB9 type of autosomal recessive non-syndromic hearing impairment (Yasunaga et al, 1999).…”

Section: Spectrum Of Otof Mutationsmentioning

confidence: 99%

“…Mutations in OTOF account for 1.4e5% of cases of autosomal recessive non-syndromic hearing impairment in the populations that have been studied to date (Choi et al, 2009;Duman et al, 2011;Hutchin et al, 2005;Iwasa et al, 2013;Jin et al, 2014;Mahdieh et al, 2012;Rodríguez-Ballesteros et al, 2003;Romanos et al, 2009;Varga et al, 2006). These mutations have been found in very different proportions in cohorts of subjects from several countries, ranging from about 5% in some Chinese and Korean studies, through 50e60% in studies from the USA, Brazil and Japan, to 86% in Spanish cohorts (Bae et al, 2013;Chiu et al, 2010;Jin et al, 2014;Matsunaga et al, 2012;Rodríguez-Ballesteros et al, 2008;Romanos et al, 2009;Varga et al, 2006;Wang et al, 2010).…”

Section: Spectrum Of Otof Mutationsmentioning

confidence: 99%

See 1 more Smart Citation

Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations

et al. 2015

View full text Add to dashboard Cite

Mutations in the OTOF gene encoding otoferlin result in a disrupted function of the ribbon synapses with an impaired multivesicular glutamate release. Most affected subjects present with congenital hearing loss and abnormal auditory brainstem potentials associated with preserved cochlear hair cell activities (otoacoustic emissions, cochlear microphonics [CMs]). Transtympanic electrocochleography (ECochG) has recently been proposed for defining the details of potentials arising in both the cochlea and auditory nerve in this disorder, and with a view to shedding light on the pathophysiological mechanisms underlying auditory dysfunction.\ud We review the audiological and electrophysiological findings in children with congenital profound deafness carrying two mutant alleles of the OTOF gene. We show that cochlear microphonic (CM) amplitude, summating potential (SP) amplitude and latency are normal, consistently with a preserved outer and inner hair cell function. In the majority of OTOF children, the SP component is followed by a markedly prolonged low-amplitude negative potential by comparison with the compound action potential (CAP) recorded in normally-hearing children. This potential is identified at intensities as low as 90 dB below the behavioral threshold. In some ears, a synchronized CAP is superimposed on the prolonged responses at high intensity. Stimulation at high rates reduces the amplitude and duration of the prolonged potentials, consistently with their neural generation. In some children, however, the ECochG response only consists of the SP, with no prolonged potential. Cochlear implants restore hearing sensitivity, speech perception and neural CAP by electrically stimulating the auditory nerve fibers.\ud These findings indicate that an impaired multivesicular glutamate release in OTOF-related disorders leads to abnormal auditory nerve fiber activation and a consequent impairment of spike generation. The magnitude of these effects seems to vary, ranging from no auditory nerve fiber activation to an abnormal generation of EPSPs that occasionally trigger a synchronized electrical activity, resulting in high-threshold CAPs

show abstract

Section: Spectrum Of Otof Mutationsmentioning

confidence: 99%

Section: Spectrum Of Otof Mutationsmentioning

confidence: 99%

Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations

et al. 2015

View full text Add to dashboard Cite

show abstract

“…So far, more than 90 pathologic mutations have been reported in OTOF [25]. The present study identified 11 possibly pathogenic OTOF variants in Japanese patients with nonsyndromic hearing loss, and 6 of them were novel mutations (p.D450E, p.W717X, p.S1368X, p.R1583H, p.V1778I, and p.E1803A).…”

Section: Discussionmentioning

confidence: 70%

OTOF mutation screening in Japanese severe to profound recessive hearing loss patients

et al. 2013

View full text Add to dashboard Cite

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

show abstract

“…To date, more than 100 pathogenic mutations related to subjects with NSHL, including ANSD, have been found in different populations [20]. The c.2485 C > T (p.Q829X) mutation was frequently found in Spanish populations and has also been observed in French, Mexicans, Argentinians and English populations [21–24].…”

Section: Discussionmentioning

confidence: 99%

Novel compound heterozygous mutations in the OTOF Gene identified by whole-exome sequencing in auditory neuropathy spectrum disorder

Tang

Wang³

et al. 2017

BMC Med Genet

View full text Add to dashboard Cite

BackgroundMany hearing-loss diseases are demonstrated to have Mendelian inheritance caused by mutations in single gene. However, many deaf individuals have diseases that remain genetically unexplained. Auditory neuropathy is a sensorineural deafness in which sounds are able to be transferred into the inner ear normally but the transmission of the signals from inner ear to auditory nerve and brain is injured, also known as auditory neuropathy spectrum disorder (ANSD). The pathogenic mutations of the genes responsible for the Chinese ANSD population remain poorly understood.MethodsA total of 127 patients with non-syndromic hearing loss (NSHL) were enrolled in Guangxi Zhuang Autonomous Region. A hereditary deafness gene mutation screening was performed to identify the mutation sites in four deafness-related genes (GJB2, GJB3, 12S rRNA, and SLC26A4). In addition, whole-exome sequencing (WES) was applied to explore unappreciated mutation sites in the cases with the singularity of its phenotype.ResultsWell-characterized mutations were found in only 8.7% (11/127) of the patients. Interestingly, two mutations in the OTOF gene were identified in two affected siblings with ANSD from a Chinese family, including one nonsense mutation c.1273C > T (p.R425X) and one missense mutation c.4994 T > C (p.L1665P). Furthermore, we employed Sanger sequencing to confirm the mutations in each subject. Two compound heterozygous mutations in the OTOF gene were observed in the two affected siblings, whereas the two parents and unaffected sister were heterozygous carriers of c.1273C > T (father and sister) and c.4994 T > C (mother). The nonsense mutation p.R425X, contributes to a premature stop codon, may result in a truncated polypeptide, which strongly suggests its pathogenicity for ANSD. The missense mutation p.L1665P results in a single amino acid substitution in a highly conserved region.ConclusionsTwo mutations in the OTOF gene in the Chinese deaf population were recognized for the first time. These findings not only extend the OTOF gene mutation spectrum for ANSD but also indicate that whole-exome sequencing is an effective approach to clarify the genetic characteristics in non-syndromic ANSD patients. Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0400-0) contains supplementary material, which is available to authorized users.

show abstract

Screening of OTOF mutations in Iran: A novel mutation and review

Cited by 32 publications

References 39 publications

Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations

Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations

OTOF mutation screening in Japanese severe to profound recessive hearing loss patients

Novel compound heterozygous mutations in the OTOF Gene identified by whole-exome sequencing in auditory neuropathy spectrum disorder

Contact Info

Product

Resources

About