OTOF-related auditory neuropathy spectrum disorder

Mr, Lalayants; Ol, Mironovich; Ea, Bliznets; Tg, Markova; Av, Polyakov; Ga, Tavartkiladze

doi:10.17116/otorino20208502121

Cited by 8 publications

(4 citation statements)

References 16 publications

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“…Auditory neuropathy spectrum disease is caused by defects in genes, which have been proven in previous studies in the recent two decades ( 3 ). Mutations in OTOF (OMIM 603681), which was the first identified gene of congenital ANSD, were the most common cause of these genetic defects ( 21 ). In previous studies, it has been elucidated that the OTOF gene located on chromosome 2p23.1 consists of 48 exons and encodes otoferlin, which is located in the basolateral region of the adult mammalian cochlea, and is mainly expressed in the inner hair cells, participates in the connection activities in afferent synapses.…”

Section: Discussionmentioning

confidence: 99%

Genetic etiological analysis of auditory neuropathy spectrum disorder by next-generation sequencing

Sun

Lin²,

Zhang³

et al. 2022

Front. Neurol.

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ObjectiveAuditory neuropathy spectrum disease (ANSD) is caused by both environmental and genetic causes and is defined by a failure in peripheral auditory neural transmission but normal outer hair cells function. To date, 13 genes identified as potentially causing ANSD have been documented. To study the etiology of ANSD, we collected 9 probands with ANSD diagnosed in the clinic and performed targeted next-generation sequencing.MethodsNine probands have been identified as ANSD based on the results of the ABR tests and DPOAE/CMs. Genomic DNA extracted from their peripheral blood was examined by next-generation sequencing (NGS) for a gene panel to identify any potential causal variations. For candidate pathogenic genes, we performed co-segregation among all family members of the pedigrees. Subsequently, using a mini-gene assay, we examined the function of a novel splice site mutant of OTOF.ResultsWe analyzed nine cases of patients with ANSD with normal CMs/DPOAE and abnormal ABR, discovered three novel mutants of the OTOF gene that are known to cause ANSD, and six cases of other gene mutations including TBC1D24, LARS2, TIMM8A, MITF, and WFS1.ConclusionOur results extend the mutation spectrum of the OTOF gene and indicate that the genetic etiology of ANSD may be related to gene mutations of TBC1D24, LARS2, TIMM8A, MITF, and WFS1.

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Section: Discussionmentioning

confidence: 99%

Genetic etiological analysis of auditory neuropathy spectrum disorder by next-generation sequencing

Sun

Lin²,

Zhang³

et al. 2022

Front. Neurol.

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“…It provides prognostic information on the possible progression of hearing loss, permits meaningful genetic counseling, and impacts treatment decisions [ 10 , 31 ]. The clinical features of hearing loss caused by STRC and USH2A gene mutations that are most frequent in the Russian population were presented in our previous papers [ 14 , 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…We enrolled 226 patients who were clinically diagnosed with sensorineural NSHL. Part of this cohort was previously described in three studies conducted by Markova et al and Lalayants et al that presented the phenotypes and the audiological features of hearing loss caused by mutations in the STRC , USH2A , and OTOF genes [ 14 , 15 , 16 ]. The current study is intended to provide an understanding of the mutation spectrum in non- GJB2 -related hearing loss in a cohort of Russian sensorineural NSHL patients and establish the best diagnostic algorithm.…”

Section: Introductionmentioning

confidence: 99%

Spectrum of Genes for Non-GJB2-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel

Shatokhina

Галеева

Степанова

et al. 2022

IJMS

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Hearing loss is one of the most genetically heterogeneous disorders known. Over 120 genes are reportedly associated with non-syndromic hearing loss (NSHL). To date, in Russia, there have been relatively few studies that apply massive parallel sequencing (MPS) methods to elucidate the genetic factors underlying non-GJB2-related hearing loss cases. The current study is intended to provide an understanding of the mutation spectrum in non-GJB2-related hearing loss in a cohort of Russian sensorineural NSHL patients and establish the best diagnostic algorithm. Genetic testing using an MPS panel, which included 33 NSHL and syndromic hearing loss (SHL) genes that might be misdiagnosed as NSHL genes, was completed on 226 sequentially accrued and unrelated patients. As a result, the molecular basis of deafness was found in 21% of the non-GJB2 NSHL cases. The total contribution pathogenic, and likely pathogenic, variants in the genes studied among all hereditary NSHL Russian patients was 12%. STRC pathogenic and likely pathogenic, variants accounted for 30% of diagnoses in GJB2-negative patients, providing the most common diagnosis. The majority of causative mutations in STRC involved large copy number variants (CNVs) (80%). Among the point mutations, the most common were c.11864G>A (p.Trp3955*) in the USH2A gene, c.2171_2174delTTTG (p.Val724Glyfs*6) in the STRC gene, and c.107A>C (p.His36Pro) and c.1001G>T (p.Gly334Val) in the SLC26A4 gene. Pathogenic variants in genes involved in SHL accounted for almost half of the cases with an established molecular genetic diagnosis, which were 10% of the total cohort of patients with non-GJB2-related hearing loss.

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“…MYO6 and MYO7A belong to the myosin family and are responsible for auditory hair cell transduction in mammals [26]. OTOF encodes otoferlin and is closely related to the synaptic transmission of auditory neurons [27]. The OTOA-encoded protein is a non-cytoglial component specific to the inner ear, and hearing impairment has been observed in mutants [24].…”

Section: Hearing Differences Of Yangtze Finless Porpoises In Differen...mentioning

confidence: 99%

Comparative Blood Transcriptome Analysis of Semi-Natural and Controlled Environment Populations of Yangtze Finless Porpoise

Liu,

Yin,

et al. 2024

Animals

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The Yangtze finless porpoises (Neophocaena asiaeorientalis asiaeorientalis) living in different environments display significant differences in behavior and physiology. To compare and analyze gene expression differences between an ex situ population and a controlled environment population of the Yangtze finless porpoise, we sequenced the transcriptome of blood tissues living in a semi-natural reserve and an artificial facility, respectively. We identified 6860 differentially expressed genes (DEGs), of which 6603 were up-regulated and 257 were down-regulated in the controlled environment vs ex situ comparison. GO and KEGG enrichment analysis showed that the up-regulated genes in the controlled environment population were significantly associated with glucose metabolism, amino acid metabolism, and the nervous system, while those up-regulated in the ex situ population were significantly associated with energy supply and biosynthesis. Further analysis showed that metabolic and hearing-related genes were significantly affected by changes in the environment, and key metabolic genes such as HK, PFK, IDH, and GLS and key hearing-related genes such as OTOA, OTOF, SLC38A1, and GABBR2 were identified. These results suggest that the controlled environment population may have enhanced glucose metabolic ability via activation of glycolysis/gluconeogenesis, the TCA cycle, and inositol phosphate metabolism, while the ex situ population may meet higher energy requirements via enhancement of the amino acid metabolism of the liver and muscle and oxidative phosphorylation. Additionally, the acoustic behavior and auditory-related genes of Yangtze finless porpoise may show responsive changes and differential expression under different environment conditions, and thus the auditory sensitivity may also show corresponding adaptive characteristics. This study provides a new perspective for further exploration of the responsive changes of the two populations to various environments and provides a theoretical reference for further improvements in conservation practices for the Yangtze finless porpoise.

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OTOF-related auditory neuropathy spectrum disorder

Cited by 8 publications

References 16 publications

Genetic etiological analysis of auditory neuropathy spectrum disorder by next-generation sequencing

Genetic etiological analysis of auditory neuropathy spectrum disorder by next-generation sequencing

Spectrum of Genes for Non-GJB2-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel

Comparative Blood Transcriptome Analysis of Semi-Natural and Controlled Environment Populations of Yangtze Finless Porpoise

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