Associations between GJB2, Mitochondrial 12S rRNA, SLC26A4 Mutations, and Hearing Loss among Three Ethnicities

Du, Wei; Wang, Qiuju; Zhu, Yiping; Wang, Yanli; Guo, Yufen

doi:10.1155/2014/746838

Cited by 21 publications

(23 citation statements)

References 26 publications

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“…Interestingly, our results showed that c.235delC also contributes to mild-to-moderate hearing loss in a significant percentage (54.05%) of such patients, with c.109G > A being another major contributor (40.54%, Table 2). In comparison with previous studies of other Chinese ethnicities such as the Uyghur population [28], the mutation spectrum of GJB2 is considerably different in Chinese Hans, as c.35delG, a common GJB2 mutation in both Uyghurs and Caucasians, was detected in only one proband in our cohort.…”

Section: Discussioncontrasting

confidence: 83%

Molecular epidemiology of Chinese Han deaf patients with bi-allelic and mono-allelic GJB2 mutations

Lin

et al. 2020

Orphanet J Rare Dis

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Background: Recessive mutations in GJB2 is the most common cause of genetic hearing loss worldwide. The aim of this study is to determine the spectrum and frequency of GJB2 variants in Chinese Han deaf patients and to investigate the underlying causative genes in patients with mono-allelic GJB2 mutations. Methods: We analyzed the mutation screening results of GJB2 in 1852 Chinese Han probands with apparently autosomal-recessive hearing loss in our laboratory. Targeted next-generation sequencing of 139 known deafnessrelated genes were performed in 44 probands with mono-allelic GJB2 mutations.Results: Bi-allelic GJB2 mutations was identified in 25.65% of patients, in which the c.235delC (p.L79Cfs*3) mutation is the most frequent cause for both severe-to-profound (84.93%) and mild-to-moderate hearing loss (54.05%), while the c.109G > A (p.V37I) mutation is another frequent cause for mild-to-moderate hearing loss (40.54%). In 3.89% of patients only one mutant allele can be identified in GJB2. Targeted next generation sequencing in 44 such probands revealed digenic heterozygous mutations in GJB2/GJB6 and GJB2/GJB3 as the likely pathogenic mechanism in three probands. In 13 probands, on the other hand, pathogenic mutations in other deafness-associated genes (STRC, EYA1, MITF, PCDH15, USH2A, MYO15A, CDH23, OTOF, SLC26A4, SMPX, and TIMM8A) can be identified as the independent genetic cause, suggesting that the mono-allelic GJB2 mutations in those probands is likely co-incidental. Conclusions: Our results demonstrated that GJB2 should be a primary target for mutation screening in Chinese Han deaf patients, and those with mono-allelic GJB2 mutations should be further screened by next generation sequencing.

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Section: Discussioncontrasting

confidence: 83%

Molecular epidemiology of Chinese Han deaf patients with bi-allelic and mono-allelic GJB2 mutations

Lin

et al. 2020

Orphanet J Rare Dis

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“…The prevalence of this allele varies highly by ethnicity. In Asian countries, the prevalence ranges between 0.6% and 14.3%, of which the lowest frequency was observed in Indian and the highest frequency was observed in Japanese populations (Fischel‐Ghodsain ; Tamagawa et al., ; Pandya et al., ; Usami et al., ; Tono et al., ; Malik et al., ; Tekin et al., ; Noguchi et al., ; Li et al., ; Padma et al., ; Kato et al., ; Lu et al., ; Ji et al., ; Wei et al., ; Zhang et al., ; Du et al., ).…”

Section: Discussionmentioning

confidence: 99%

Genetic Epidemiology of Mitochondrial Pathogenic Variants Causing Nonsyndromic Hearing Loss in a Large Cohort of South Indian Hearing Impaired Individuals

Subathra

Ramesh

Selvakumari

et al. 2016

Annals of Human Genetics

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Mitochondria play a critical role in the generation of metabolic energy in the form of ATP. Tissues and organs that are highly dependent on aerobic metabolism are involved in mitochondrial disorders including nonsyndromic hearing loss (NSHL). Seven pathogenic variants leading to NSHL have so far been reported on two mitochondrial genes: MT-RNR1 encoding 12SrRNA and MT-TS1 encoding tRNA for Ser((UCN)) . We screened 729 prelingual NSHL subjects to determine the prevalence of MT-RNR1 variants at position m.961, m.1555A>G and m.1494C>T, and MT-TS1 m.7445A>G, m.7472insC m.7510T>C and m.7511T>C variants. Mitochondrial pathogenic variants were found in eight probands (1.1%). Five of them were found to have the m.1555A>G variant, two others had m.7472insC and one proband had m.7444G>A. The extended relatives of these probands showed variable degrees of hearing loss and age at onset. This study shows that mitochondrial pathogenic alleles contribute to about 1% prelingual hearing loss. This study will henceforth provide the reference for the prevalence of mitochondrial pathogenic alleles in the South Indian population, which to date has not been estimated. The m.1555A>G variant is a primary predisposing genetic factor for the development of hearing loss. Our study strongly suggests that mitochondrial genotyping should be considered for all hearing impaired individuals and particularly in families where transmission is compatible with maternal inheritance, after ruling out the most common variants.

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“…pre-screening, the percentages increased slightly (22%, 16%, 0%, 45%, and 17%, respectively), which is in agreement with other reports (Bazazzadegan et al 2012;Dai et al 2009;Du et al 2014;Pandya et al 2003;Usami et al 2012 Of variants with a MAF of <0.01, the largest majority were of unknown significance (VUSs, Figure 3.2). In addition, however, we identified several known or likely pathogenic variants associated with ARNSHL in genes without a second causal variant.…”

Section: Discussionsupporting

confidence: 90%

Precision health and deafness–optimizing genetic diagnosis

Sloan-Heggen¹

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Associations between GJB2, Mitochondrial 12S rRNA, SLC26A4 Mutations, and Hearing Loss among Three Ethnicities

Cited by 21 publications

References 26 publications

Molecular epidemiology of Chinese Han deaf patients with bi-allelic and mono-allelic GJB2 mutations

Molecular epidemiology of Chinese Han deaf patients with bi-allelic and mono-allelic GJB2 mutations

Genetic Epidemiology of Mitochondrial Pathogenic Variants Causing Nonsyndromic Hearing Loss in a Large Cohort of South Indian Hearing Impaired Individuals

Precision health and deafness–optimizing genetic diagnosis

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