Common Molecular Etiologies Are Rare in Nonsyndromic Tibetan Chinese Patients with Hearing Impairment

Yuan, Yongyi; Zhang, Xun; Huang, Shasha; Zuo, Lujie; Zhang, Guozheng; Song, Yue-shuai; Wang, Guojian; Wang, Hong-tian; Huang, Deliang; Han, Dongyi; Dai, Pu

doi:10.1371/journal.pone.0030720

Cited by 27 publications

(23 citation statements)

References 49 publications

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“…Our results also revealed that the SLC26A4 detection rate and incidence of EVA varied geographically. The incidence of inner ear malformation in the Tibetans living in the Tibet plateau was almost as high as that in Chinese Han patients, but the types of malformation in the Tibetan population differed greatly [32]. The most-common inner ear deformity, EVA, is rare in the Chinese Tibetan hearing-loss population.…”

Section: Discussionmentioning

confidence: 96%

Molecular Epidemiology and Functional Assessment of Novel Allelic Variants of SLC26A4 in Non-Syndromic Hearing Loss Patients with Enlarged Vestibular Aqueduct in China

et al. 2012

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BackgroundMutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations are responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA). The mutation spectrum of SLC26A4 varies widely among ethnic groups. To investigate the incidence of EVA in Chinese population and to provide appropriate genetic testing and counseling to patients with SLC26A4 variants, we conducted a large-scale molecular epidemiological survey of SLC26A4.MethodsA total of 2352 unrelated non-syndromic hearing loss patients from 27 different regions of China were included. Hot spot regions of SLC26A4, exons 8, 10 and 19 were sequenced. For patients with one allelic variant in the hot spot regions, the other exons were sequenced one by one until two mutant alleles had been identified. Patients with SLC26A4 variants were then examined by temporal bone computed tomography scan for radiological diagnosis of EVA. Ten SLC26A4 variants were cloned for functional study. Confocal microscopy and radioisotope techniques were used to examine the membrane expression of pendrin and transporter function.ResultsOf the 86 types of variants found, 47 have never been reported. The ratio of EVA in the Chinese deaf population was at least 11%, and that in patients of Han ethnicity reached at least 13%. The mutational spectrum and mutation detection rate of SLC26A4 are distinct among both ethnicities and regions of Mainland China. Most of the variants caused retention of pendrin in the intracellular region. All the mutant pendrins showed significantly reduced transport capability.ConclusionAn overall description of the molecular epidemiological findings of SLC26A4 in China is provided. The functional assessment procedure can be applied to identification of pathogenicity of variants. These findings are valuable for genetic diagnosis, genetic counseling, prenatal testing and pre-implantation diagnosis in EVA families.

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Section: Discussionmentioning

confidence: 96%

Molecular Epidemiology and Functional Assessment of Novel Allelic Variants of SLC26A4 in Non-Syndromic Hearing Loss Patients with Enlarged Vestibular Aqueduct in China

et al. 2012

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“…However, this mutation was not found in the 300 healthy individuals. A previous study has shown that c.109G>A was a polymorphism (Yuan et al, 2012), but another study claimed that it is pathogenic. In the study, compound heterozygous mutations in GJB2 were found in four patients.…”

Section: Discussionmentioning

confidence: 99%

“…Four patients showed compound heterozygous mutations carrying c.35delG;c.235delC, c. c.35delG;and c.235delC;respectively. Among the 300 healthy individuals, only two subjects were found to carry heterozygous pathogenic mutation c.235delC with a frequency of 0.67% (2/300); two other variants, c.79G>A and c.341A>G, accounted for 28.67% (86/300) and 14.00% (42/300), respectively. c.79G>A and c.341A>G were polymorphisms that could lead to nonsynonymous changes: p.V27I and p.E114G, respectively (Yuan et al, 2012).…”

Section: Gjb2 Mutationsmentioning

confidence: 99%

Mutation analysis of common deafness genes among 1,201 patients with non‐syndromic hearing loss in Shanxi Province

Zhou

et al. 2019

Molec Gen & Gen Med

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Background Hearing impairment is one of most frequent birth defects, which affects nearly 1 in every 1,000 live births. However, the molecular etiology of non‐syndromic deafness in China is not well studied. Here, we have investigated the presence of mutations in three genes commonly mutated in non‐syndromic deafness patients in Shanxi Province, which has the highest frequency of birth defects in China. Methods In total, 1,201 unrelated non‐syndromic deafness patients and 300 healthy individuals were enrolled. The hearing ability was confirmed by audiologic evaluation. Three major deafness‐related genes ( GJB2, SLC26A4 (PDS), and mtDNA 12S rRNA ) of all individuals enrolled were analyzed by Sanger sequencing. Results The results showed that GJB2 mutations accounted for 21.23% (255/1,201) in the patient group, with c.235delC, a hotspot mutation, accounting for 10.99% (132/1,201). Moreover, 11 new GJB2 mutations were identified. SLC26A4 mutations accounted for 9.33% (112/1,201) in the patient group, with IVS7‐2A>G as the most prevalent mutation accounting for 4.75% (57/1,201). In addition, 15 patients (1.25%) were found to carry mtDNA 12S rRNA c.1555A>G mutation, while only two cases had the mtDNA 12S rRNA c.1494C>T. Conclusion In our research, it was found that c.235delC in GJB2 and c.919‐2A>G (IVS7‐2A>G) in SLC26A4 were the highest frequency pathogenic variants in Shanxi Province. Taken together, our data will enrich the database of deafness mutations and will help clinical diagnosis, treatment, and genetic counseling of hearing impairment.

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“…Previous reports suggest that there is a difference in the prevalence of the 1555A > G mutation among different ethnicities. It was estimated at 8.56% in the northern region with a frequency of 0-3.92% among Uyghurs and 0-1.75% in Tibetans (Li et al, 2010b;Yuan et al, 2012). We speculate that there are several reasons for the racial diversity of hearing levels among the 1555A > G mutation frequencies, such as aminoglycoside antibiotics abuse, some modifying factors increasing the deafness penetrance of mtDNA mutations, and smaller population, but higher endogamy rate in the multiethnic minorities.…”

Section: Figmentioning

confidence: 99%

Prevalence of Mutations in GJB2, SLC26A4, and mtDNA in Children with Severe or Profound Sensorineural Hearing Loss in Southwestern China

Zhou

Lai

et al. 2015

Genetic Testing and Molecular Biomarkers

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Aim: To study the distribution characteristics of common mutations in the GJB2, SLC26A4, and mtDNA genes in children with severe or profound sensorineural hearing loss (SNHL) in southwestern China. Materials and Methods: A total of 1,164 individuals were recruited to screen for the common GJB2, SLC26A4, and mtDNA mutations by microarrays. Subsequencing for the coding region of the GJB2 gene in the samples without the GJB2 hotspot mutations as well as subsequencing for the exon 1 of the TRMU gene in those samples with the mtDNA hotspot mutations was performed by Sanger sequencing. All mutations were analyzed in association with medical imaging. Results: In this study, 28.43% of all subjects carried mutations. The mutation frequencies in the GJB2, SLC26A4, and mtDNA genes were 17.27%, 7.04%, and 4.12%, respectively. No TRMU mutation was found in the study. The frequency of the mtDNA mutations in the multiethnic minorities was six times that in the Han (11.23% vs. 1.91%; p approaches 0.000) and in the urban group was one-third of that in the suburban group(1.49% vs. 4.47%; p = 0.047). The frequency of the GJB2 mutations in urban and suburban groups was 23.38% and 15.99%, respectively ( p = 0.012). The enlarged vestibular aqueduct (EVA) was the most common inner ear malformation and *79.10% of EVA cases were associated with the SLC26A4 mutations. Conclusions: More than one-fourth of children with severe or profound SNHL carried the common deafness mutations. The proportions of ethnic minorities and urban subjects could impact the frequency of the GJB2 and mtDNA mutations. The SLC26A4 hotspot mutations are prevalent and correlate strongly with EVA.

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Common Molecular Etiologies Are Rare in Nonsyndromic Tibetan Chinese Patients with Hearing Impairment

Cited by 27 publications

References 49 publications

Molecular Epidemiology and Functional Assessment of Novel Allelic Variants of SLC26A4 in Non-Syndromic Hearing Loss Patients with Enlarged Vestibular Aqueduct in China

Molecular Epidemiology and Functional Assessment of Novel Allelic Variants of SLC26A4 in Non-Syndromic Hearing Loss Patients with Enlarged Vestibular Aqueduct in China

Mutation analysis of common deafness genes among 1,201 patients with non‐syndromic hearing loss in Shanxi Province

Prevalence of Mutations in GJB2, SLC26A4, and mtDNA in Children with Severe or Profound Sensorineural Hearing Loss in Southwestern China

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