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Mutation Spectrum of Common Deafness-Causing Genes in Patients with Non-Syndromic Deafness in the Xiamen Area, China.

Jiang Y, Huang S, Deng T, Wu L, Chen J, Kang D, Xu X, Li R, Han D, Dai P - PLoS ONE (2015)

Bottom Line: The non-syndromic hearing loss (NSHL) hotspot mutations c.109G>A (p.V37I) and c.235delC were found in this population, whereas the Caucasian hotspot mutation c.35delG was not.The allelic frequency of the c.109G>A mutation was significantly higher in this Xiamen's deaf population than that in previously reported cohorts (P = 0.00).The SLC26A4 mutations were found in 16.77% (26/155) of this cohort.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China; Fujian Medical University ShengLi clinical college, Fujian Provincial Hospital, Fuzhou, P. R. China.

ABSTRACT
In China, approximately 30,000 babies are born with hearing impairment each year. However, the molecular factors causing congenital hearing impairment in the Xiamen area of Fujian province have not been evaluated. To provide accurate genetic testing and counseling in the Xiamen area, we investigated the molecular etiology of non-syndromic deafness in a deaf population from Xiamen. Unrelated students with hearing impairment (n = 155) who attended Xiamen Special Education School in Fujian Province were recruited for this study. Three common deafness-related genes, GJB2, SLC26A4, and mtDNA12SrRNA, were analyzed using all-exon sequencing. GJB2 mutations were detected in 27.1% (42/155) of the entire cohort. The non-syndromic hearing loss (NSHL) hotspot mutations c.109G>A (p.V37I) and c.235delC were found in this population, whereas the Caucasian hotspot mutation c.35delG was not. The allelic frequency of the c.109G>A mutation was 9.03% (28/310), slightly higher than that of c.235delC (8.39%, 26/310), which is the most common GJB2 mutation in most areas of China. The allelic frequency of the c.109G>A mutation was significantly higher in this Xiamen's deaf population than that in previously reported cohorts (P = 0.00). The SLC26A4 mutations were found in 16.77% (26/155) of this cohort. The most common pathogenic allele was c.IVS7-2A>G (6.13%, 19/310), and the second most common was the c.1079C>T (p.A360V) mutation (1.94%, 6/310) which has rarely been reported as a hotspot mutation in other studies. The mutation rate of mtDNA12SrRNA in this group was 3.87% (6/155), all being the m.A1555G mutation. These findings show the specificity of the common deaf gene-mutation spectrum in this area. According to this study, there were specific hotspot mutations in Xiamen deaf patients. Comprehensive sequencing analysis of the three common deaf genes can help portray the mutation spectrum and develop optimal testing strategies for deaf patients in this area.

No MeSH data available.


Related in: MedlinePlus

Protein alignment showing conservation of residues GJB2 V670 across six species.An alignment of the SLC26A4 amino acid sequence of six species suggested the evolutionary conservation of c.2009T>C (p.V670A).
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pone.0135088.g001: Protein alignment showing conservation of residues GJB2 V670 across six species.An alignment of the SLC26A4 amino acid sequence of six species suggested the evolutionary conservation of c.2009T>C (p.V670A).

Mentions: This variant was not found in 1,668 EVAS patients from our laboratory before this study, and the mutation frequency of c.2009T>C in this Xiamen’s cohort was 1.29% (2/155). We predicted the pathogenicity of this mutation by SIFT and Polyphen-2, and the results suggested “tolerant,” with a SIFT score of 0.05 and “possibly damaging” with a Polyphen-2 score of 0.873 by each. We made an alignment of the SLC26A4 amino acid sequence of six species, namely Homo sapiens (043511), Macaca mulatta (XP_001094049.1), Mus musculus (NP_035997.1), Rattus norvegicus (NP_062087.1), Bos taurus (XP_608706.3), and Sus scrofa (XP_003357559.1) (Fig 1), and the results suggested the evolutionary conservation of c.2009T>C. However, only two of 155 patients (1.29%) were found to carry the heterozygote of this variant in the present study; thus, a conclusion still cannot be reached.


Mutation Spectrum of Common Deafness-Causing Genes in Patients with Non-Syndromic Deafness in the Xiamen Area, China.

Jiang Y, Huang S, Deng T, Wu L, Chen J, Kang D, Xu X, Li R, Han D, Dai P - PLoS ONE (2015)

Protein alignment showing conservation of residues GJB2 V670 across six species.An alignment of the SLC26A4 amino acid sequence of six species suggested the evolutionary conservation of c.2009T>C (p.V670A).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4529078&req=5

pone.0135088.g001: Protein alignment showing conservation of residues GJB2 V670 across six species.An alignment of the SLC26A4 amino acid sequence of six species suggested the evolutionary conservation of c.2009T>C (p.V670A).
Mentions: This variant was not found in 1,668 EVAS patients from our laboratory before this study, and the mutation frequency of c.2009T>C in this Xiamen’s cohort was 1.29% (2/155). We predicted the pathogenicity of this mutation by SIFT and Polyphen-2, and the results suggested “tolerant,” with a SIFT score of 0.05 and “possibly damaging” with a Polyphen-2 score of 0.873 by each. We made an alignment of the SLC26A4 amino acid sequence of six species, namely Homo sapiens (043511), Macaca mulatta (XP_001094049.1), Mus musculus (NP_035997.1), Rattus norvegicus (NP_062087.1), Bos taurus (XP_608706.3), and Sus scrofa (XP_003357559.1) (Fig 1), and the results suggested the evolutionary conservation of c.2009T>C. However, only two of 155 patients (1.29%) were found to carry the heterozygote of this variant in the present study; thus, a conclusion still cannot be reached.

Bottom Line: The non-syndromic hearing loss (NSHL) hotspot mutations c.109G>A (p.V37I) and c.235delC were found in this population, whereas the Caucasian hotspot mutation c.35delG was not.The allelic frequency of the c.109G>A mutation was significantly higher in this Xiamen's deaf population than that in previously reported cohorts (P = 0.00).The SLC26A4 mutations were found in 16.77% (26/155) of this cohort.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China; Fujian Medical University ShengLi clinical college, Fujian Provincial Hospital, Fuzhou, P. R. China.

ABSTRACT
In China, approximately 30,000 babies are born with hearing impairment each year. However, the molecular factors causing congenital hearing impairment in the Xiamen area of Fujian province have not been evaluated. To provide accurate genetic testing and counseling in the Xiamen area, we investigated the molecular etiology of non-syndromic deafness in a deaf population from Xiamen. Unrelated students with hearing impairment (n = 155) who attended Xiamen Special Education School in Fujian Province were recruited for this study. Three common deafness-related genes, GJB2, SLC26A4, and mtDNA12SrRNA, were analyzed using all-exon sequencing. GJB2 mutations were detected in 27.1% (42/155) of the entire cohort. The non-syndromic hearing loss (NSHL) hotspot mutations c.109G>A (p.V37I) and c.235delC were found in this population, whereas the Caucasian hotspot mutation c.35delG was not. The allelic frequency of the c.109G>A mutation was 9.03% (28/310), slightly higher than that of c.235delC (8.39%, 26/310), which is the most common GJB2 mutation in most areas of China. The allelic frequency of the c.109G>A mutation was significantly higher in this Xiamen's deaf population than that in previously reported cohorts (P = 0.00). The SLC26A4 mutations were found in 16.77% (26/155) of this cohort. The most common pathogenic allele was c.IVS7-2A>G (6.13%, 19/310), and the second most common was the c.1079C>T (p.A360V) mutation (1.94%, 6/310) which has rarely been reported as a hotspot mutation in other studies. The mutation rate of mtDNA12SrRNA in this group was 3.87% (6/155), all being the m.A1555G mutation. These findings show the specificity of the common deaf gene-mutation spectrum in this area. According to this study, there were specific hotspot mutations in Xiamen deaf patients. Comprehensive sequencing analysis of the three common deaf genes can help portray the mutation spectrum and develop optimal testing strategies for deaf patients in this area.

No MeSH data available.


Related in: MedlinePlus