Novel Compound Heterozygous TMC1 Mutations Associated with Autosomal Recessive Hearing Loss in a Chinese Family

Gao, Xue; Su, Yu; Guan, Liping; Yuan, Yongyi; Huang, Shasha; Lu, Yu; Wang, Guojian; Han, Mingyu; Yu, Fei; Song, Yue-shuai; Zhu, Qingyan; Wu, Jing; Dai, Pu

doi:10.1371/journal.pone.0063026

Cited by 29 publications

(30 citation statements)

References 32 publications

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“…These families have their origins in Pakistan, Turkey, Tunisia, Iran, Lebanon/Jordan, North America, China, Europe, Sudan and Morocco (Table 2) [23,35,37–48]. These 39 mutations are widely distributed throughout the entire coding region of TMC1 .…”

Section: Phenotype and Mutation Spectrum Of Dfnb7/b11 Subjectsmentioning

confidence: 99%

Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction

Nakanishi¹,

Kurima²,

Kawashima³

et al. 2014

Auris Nasus Larynx

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Objective Mutations of transmembrane channel-like 1 gene (TMC1) can cause dominant (DFNA36) or recessive (DFNB7/B11) deafness. In this article, we describe the characteristics of DFNA36 and DFNB7/B11 deafness, the features of the Tmc1 mutant mouse strains, and recent advances in our understanding of TMC1 function. Methods Publications related to TMC1, DFNA36 or DFNB7/B11 were identified through PubMed. Results All affected DFNA36 subjects showed post-lingual, progressive, sensorineural hearing loss (HL), initially affecting high frequencies. In contrast, almost all affected DFNB7/B11 subjects demonstrated congenital or prelingual severe to profound sensorineural HL. The mouse Tmc1 gene also has dominant and recessive mutant alleles that cause HL in mutant strains, including Beethoven, deafness and Tmc1 knockout mice. These mutant mice have been instrumental for revealing that Tmc1 and its closely related paralog Tmc2 are expressed in cochlear and vestibular hair cells, and are required for hair cell mechanoelectrical transduction (MET). Recent studies suggest that TMC1 and TMC2 may be components of the long-sought hair cell MET channel. Conclusion TMC1 mutations disrupt hair cell MET.

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Section: Phenotype and Mutation Spectrum Of Dfnb7/b11 Subjectsmentioning

confidence: 99%

Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction

Nakanishi¹,

Kurima²,

Kawashima³

et al. 2014

Auris Nasus Larynx

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“…In China, recent studies on TMC1 mutations such as c.589G>A, c.1171C>T (Xue et al, 2013), c.1209G>C (Tao et al, 2013Tao, Xiaoming, Yongchuan, Lei, & Hao, 2013), c.1253T>A (Yali et al, 2014), c.1714G>A (Xue et al, 2015), and c.1979C>T (Jiongjiong et al, 2016) have been reported. All mutations were analyzed by genetic testing of sporadic families without regional specificity.…”

Section: Discussionmentioning

confidence: 99%

“…The protein, which functions as an ion channel or transporter to mediate K+ homeostasis for the normal function of cochlear hair cells, consists of 760 amino acids containing six transmembrane (TM) domains (Xue et al, 2013). TMC1 c.2050G>C (p.D684H) is a missense variant in exon21.…”

Section: Introductionmentioning

confidence: 99%

Mutation spectra and founder effect of TMC1 in patients with non‐syndromic deafness in Xiamen area, China

Jiang

Gao

et al. 2017

American J of Med Genetics Pt B

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To analyze the spectrum and founder effect of TMC1 mutations in patients with non‐syndromic deafness in the Xiamen area. Sporadic pedigrees were detected by targeted next‐generation sequencing, and 110 unrelated patients from Xiamen Special Education School were analyzed through Sanger sequencing for the TMC1 gene. In total, 53 SNPs were designed to analyze the haplotypes of the TMC1 c.2050G>C mutation. The probands of three families were found to be homozygous for TMC1 c.2050G>C, and their parents were all heterozygous for the TMC1 c.2050G>C mutation. In 110 unrelated patients from Xiamen Special Education School, four were found to carry compound heterozygotes of TMC1 c.2050G>C, which were compound heterozygotes of c.804G>A, c.1127T>C, c.1165C>T, and c.1396_1398delAAC, respectively. Three types of TMC1 polymorphisms (c.45C>T, c.1713C>T, c.2208+49C>T) and two heterozygotes of novel variants (c.1764‐4C>A, c.2073G>A[p.K691K]) were found in the remaining 100 patients. In total, four novel variants were detected in this study. These mutations and variants were not detected in 100 normal samples. The haplotypes of the probands of families with TMC1 c.2050G>C were identical. There were unique hotspots and spectra of TMC1 mutations in the Xiamen deaf population. Haplotype analysis is useful to understand the founder effect of the hot spot mutation.

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“…Single-nucleotide polymorphism (SNP) analysis was performed as previously described (Gao et al, 2013): (1) reads were aligned to the NCBI human reference genome (gh19/NCBI 37.1) with SOAPaligner method V2.21; (2) for paired-end reads with duplicated start and end sites, only one copy with the highest quality was retained and the reads with adapters were removed; (3) SOAPsnp V1.05 was used to assemble the consensus sequence and call genotypes; (4) small insertions and deletions (INDELs) detection was used with the Unified Genotyper tool from GATK V1.0.4705.…”

Section: Read Mapping and Variant Detectionmentioning

confidence: 99%

“…Five major steps were taken to prioritize all the high-quality variants among CHD-related genes (Gao et al, 2013): (1) variants within intergenic, intronic, and untranslated regions (UTRs) and synonymous mutations were excluded from later analysis; (2) variants in dbSNP132 (http://www.ncbi.nih.gov/ projects/SNP/), the 1000 Genomes project (1000G, http://www.1000genomes.org), and HapMap project (ftp://ftp.ncbi.nlm.nih.gov/hapmap) were excluded; (3) variants in YH database (http://yh.Genomics. org.cn/) and National Heart, Lung, and Blood Institute (NHLBI) ESP database (http://evs.gs.washington.…”

Section: Filtering and Annotationmentioning

confidence: 99%

A novel variant in TBX20 (p.D176N) identified by whole-exome sequencing in combination with a congenital heart disease related gene filter is associated with familial atrial septal defect

Liu

Fan

Chen

et al. 2014

J. Zhejiang Univ. Sci. B

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Liu et al. / J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2014 15(9):830-837 830 A novel variant in TBX20 (p.D176N) identified by whole-exome sequencing in combination with a congenital heart disease related gene filter is associated with familial atrial septal defect Abstract: Congenital heart disease (CHD) is the leading cause of birth defects, and its etiology is not completely understood. Atrial septal defect (ASD) is one of the most common defects of CHD. Previous studies have demonstrated that mutations in the transcription factor T-box 20 (TBX20) contribute to congenital ASD. Whole-exome sequencing in combination with a CHD-related gene filter was used to detect a family of three generations with ASD. A novel TBX20 mutation, c.526G>A (p.D176N), was identified and co-segregated in all affected members in this family. This mutation was predicted to be deleterious by bioinformatics programs (SIFT, Polyphen2, and MutationTaster). This mutation was also not presented in the current Single Nucleotide Polymorphism Database (dbSNP) or National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP). In conclusion, our finding expands the spectrum of TBX20 mutations and provides additional support that TBX20 plays important roles in cardiac development. Our study also provided a new and cost-effective analysis strategy for the genetic study in small CHD pedigree.

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Novel Compound Heterozygous TMC1 Mutations Associated with Autosomal Recessive Hearing Loss in a Chinese Family

Cited by 29 publications

References 32 publications

Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction

Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction

Mutation spectra and founder effect of TMC1 in patients with non‐syndromic deafness in Xiamen area, China

A novel variant in TBX20 (p.D176N) identified by whole-exome sequencing in combination with a congenital heart disease related gene filter is associated with familial atrial septal defect

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