Whole exome analysis of patients in Japan with hearing loss reveals high heterogeneity among responsible and novel candidate genes

Mutai, Hideki; Momozawa, Yukihide; Kamatani, Yoichiro; Nakano, Atsuko; Sakamoto, Hirokazu; Takiguchi, Tetsuya; Nara, Kiyomitsu; Kubo, Michiaki; Matsunaga, Tatsuo

doi:10.1186/s13023-022-02262-4

Cited by 4 publications

(2 citation statements)

References 89 publications

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“…These findings align with previous research, highlighting the limitations of WES in identifying pathogenic mutations in all affected individuals, particularly in sporadic cases. For instance, a study by Mutai et al in 2022 successfully identified the responsible gene in 21 out of 72 cases (approximately 29%) using WES [66]. Similarly, Reiss et al demonstrated that WES analysis of 71 probands with hearing loss revealed pathogenic or likely pathogenic variants in only 21.1% of cases [67].…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of 106 sporadic cases with hearing loss in the UAE population

Tlili,

Mahfood,

Al Mutery

et al. 2024

Hum Genomics

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Background Hereditary hearing loss is a rare hereditary condition that has a significant presence in consanguineous populations. Despite its prevalence, hearing loss is marked by substantial genetic diversity, which poses challenges for diagnosis and screening, particularly in cases with no clear family history or when the impact of the genetic variant requires functional analysis, such as in the case of missense mutations and UTR variants. The advent of next-generation sequencing (NGS) has transformed the identification of genes and variants linked to various conditions, including hearing loss. However, there remains a high proportion of undiagnosed patients, attributable to various factors, including limitations in sequencing coverage and gaps in our knowledge of the entire genome, among other factors. In this study, our objective was to comprehensively identify the spectrum of genes and variants associated with hearing loss in a cohort of 106 affected individuals from the UAE. Results In this study, we investigated 106 sporadic cases of hearing impairment and performed genetic analyses to identify causative mutations. Screening of the GJB2 gene in these cases revealed its involvement in 24 affected individuals, with specific mutations identified. For individuals without GJB2 mutations, whole exome sequencing (WES) was conducted. WES revealed 33 genetic variants, including 6 homozygous and 27 heterozygous DNA changes, two of which were previously implicated in hearing loss, while 25 variants were novel. We also observed multiple potential pathogenic heterozygous variants across different genes in some cases. Notably, a significant proportion of cases remained without potential pathogenic variants. Conclusions Our findings confirm the complex genetic landscape of hearing loss and the limitations of WES in achieving a 100% diagnostic rate, especially in conditions characterized by genetic heterogeneity. These results contribute to our understanding of the genetic basis of hearing loss and emphasize the need for further research and comprehensive genetic analyses to elucidate the underlying causes of this condition.

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Section: Discussionmentioning

confidence: 99%

Genetic analysis of 106 sporadic cases with hearing loss in the UAE population

Tlili,

Mahfood,

Al Mutery

et al. 2024

Hum Genomics

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“…Wu Jie used targeted genome sequencing to make molecular diagnosis for a large number of hearing loss people ( Wu et al, 2022 ). Mutai Hideki analyzed the whole exome analysis of Japanese hearing loss patients, which showed a high degree of heterogeneity between responsible and new candidate genes ( Mutai et al, 2022 ). Cesca Federica analysised of the frequency of Usher gene mutations in non-syndromic hearing loss ( Cesca et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Preliminary investigation of the diagnosis and gene function of deep learning PTPN11 gene mutation syndrome deafness

Huang²,

Huang³

et al. 2023

Front. Genet.

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Syndromic deafness caused by PTPN11 gene mutation has gradually come into the public’s view. In the past, many people did not understand its application mechanism and role and only focused on non-syndromic deafness, so the research on syndromic deafness is not in-depth and there is a large degree of lack of research in this area. In order to let the public know more about the diagnosis and gene function of deafness caused by PTPN11 gene mutation syndrome, this paper used deep learning technology to study the diagnosis and gene function of deafness caused by syndrome with the concept of intelligent medical treatment, and finally drew a feasible conclusion. This paper provided a theoretical and practical basis for the diagnosis of deafness caused by PTPN11 gene mutation syndrome and the study of gene function. This paper made a retrospective analysis of the clinical data of 85 deaf children who visited Hunan Children’s Hospital,P.R. China from January 2020 to December 2021. The conclusion were as follows: Children aged 1–6 years old had multiple syndrome deafness, while children under 1 year old and children aged 6–12 years old had relatively low probability of complex deafness; girls were not easy to have comprehensive deafness, but there was no specific basis to prove that the occurrence of comprehensive deafness was necessarily related to gender; the hearing loss of patients with Noonan Syndrome was mainly characterized by moderate and severe damage and abnormal inner ear and auditory nerve; most of the mutation genes in children were located in Exon1 and Exon3, with a total probability of 57.65%. In the course of the experiment, it was found that deep learning was effective in the diagnosis of deafness with PTPN11 gene mutation syndrome. This technology could be applied to medical diagnosis to facilitate the diagnosis and treatment of more patients with deafness with syndrome. Intelligent medical treatment was also becoming a hot topic nowadays. By using this concept to analyze and study the pathological characteristics of deafness caused by PTPN11 gene mutation syndrome, it not only promoted patients to find diseases in time, but also helped doctors to diagnose and treat such diseases, which was of great significance to patients and doctors. The study of PTPN11 gene mutation syndrome deafness was also of great significance in genetics. The analysis of its genes not only enriched the gene pool, but also provided reference for future research.

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The many faces of the zinc finger protein 335 in brain development and immune system

Quan

et al. 2023

Biomedicine & Pharmacotherapy

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Whole exome analysis of patients in Japan with hearing loss reveals high heterogeneity among responsible and novel candidate genes

Cited by 4 publications

References 89 publications

Genetic analysis of 106 sporadic cases with hearing loss in the UAE population

Genetic analysis of 106 sporadic cases with hearing loss in the UAE population

Preliminary investigation of the diagnosis and gene function of deep learning PTPN11 gene mutation syndrome deafness

The many faces of the zinc finger protein 335 in brain development and immune system

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