Full Text:   <783>

Summary:  <109>

Suppl. Mater.: 

CLC number: R394; R764

On-line Access: 2019-01-22

Received: 2017-12-20

Revision Accepted: 2018-03-07

Crosschecked: 2018-08-14

Cited: 0

Clicked: 1630

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Ye Chen

https://orcid.org/0000-0003-3671-2504

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.2 P.164-169

10.1631/jzus.B1700185


New SNP variants of MARVELD2 (DFNB49) associated with non-syndromic hearing loss in Chinese population


Author(s):  Jing Zheng, Wen-fang Meng, Chao-fan Zhang, Han-qing Liu, Juan Yao, Hui Wang, Ye Chen, Min-xin Guan

Affiliation(s):  Division of Medical Genetics and Genomics, the Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; more

Corresponding email(s):   yechency@zju.edu.cn

Key Words:  Chinese population, MARVELD2, Non-Syndromic Hearing Loss, SNP variants


Jing Zheng, Wen-fang Meng, Chao-fan Zhang, Han-qing Liu, Juan Yao, Hui Wang, Ye Chen, Min-xin Guan. New SNP variants of MARVELD2 (DFNB49) associated with non-syndromic hearing loss in Chinese population[J]. Journal of Zhejiang University Science B, 2019, 20(2): 164-169.

@article{title="New SNP variants of MARVELD2 (DFNB49) associated with non-syndromic hearing loss in Chinese population",
author="Jing Zheng, Wen-fang Meng, Chao-fan Zhang, Han-qing Liu, Juan Yao, Hui Wang, Ye Chen, Min-xin Guan",
journal="Journal of Zhejiang University Science B",
volume="20",
number="2",
pages="164-169",
year="2019",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1700185"
}

%0 Journal Article
%T New SNP variants of MARVELD2 (DFNB49) associated with non-syndromic hearing loss in Chinese population
%A Jing Zheng
%A Wen-fang Meng
%A Chao-fan Zhang
%A Han-qing Liu
%A Juan Yao
%A Hui Wang
%A Ye Chen
%A Min-xin Guan
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 2
%P 164-169
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1700185

TY - JOUR
T1 - New SNP variants of MARVELD2 (DFNB49) associated with non-syndromic hearing loss in Chinese population
A1 - Jing Zheng
A1 - Wen-fang Meng
A1 - Chao-fan Zhang
A1 - Han-qing Liu
A1 - Juan Yao
A1 - Hui Wang
A1 - Ye Chen
A1 - Min-xin Guan
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 2
SP - 164
EP - 169
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1700185


Abstract: 
non-Syndromic Hearing Loss (NSHL) is a common defect in humans. Variants of MARVELD2 at the DFNB49 locus have been shown to cause bilateral, moderate to profound NSHL. However, the role of MARVELD2 in NSHL susceptibility in the chinese population has not been studied. Here we conducted a case-control study in an eastern chinese population to profile the spectrum and frequency of MARVELD2 variants, as well as the association of MARVELD2 gene variants with NSHL. Our results showed that variants identified in the chinese population are significantly different from those reported in Slovak, Hungarian, and Czech Roma, as well as Pakistani families. We identified 11 variants in a cohort of 283 NSHL cases. Through Sanger sequencing and bioinformatics analysis, we found that c.730G>A variant has detrimental effects in the eastern chinese population, and may have relatively high correlation with NSHL pathogenicity.

中国人群中非综合征耳聋相关MARVELD2 (DFNB49)基因新单核苷酸多态性位点分析

目的:探究MARVELD2在中国非综合征耳聋(NSHL)人群中的突变频谱和突变频率.
创新点:发现MARVELD2突变频谱具有明显种族特异性.中国NSHL人群中的突变位点及频率不同于已报道的其他人群,并首次筛选到新致聋候选突变MARVELD2 c.730G>A.本研究有助于进一步阐释MARVELD2在NSHL中的作用.
方法:收集283例NSHL患者外周血,提取基因组DNA,涉及9对引物覆盖MARVELD2基因编码区,经聚合酶链反应(PCR)扩增后Sanger测序.测序结果与参考序列比对,获得的MARVELD2变异位点通过正常人群频率比较、氨基酸保守性分析、氨基酸性质分析、SIFT和PolyPhen有害性预测及蛋白结构功能预测分析等进一步筛选得到耳聋候选突变位点.
结论:中国NSHL人群的MARVELD2突变位点与巴基斯坦人群,以及斯洛伐克、匈牙利和捷克罗马人群不同,具有明显的种族特异性.本研究在283个NSHL病例中共鉴定了11个变异位点.其中,c.730G>A突变可能影响MARVELD2蛋白的正常功能,与NSHL致病有较高的相关性,是一个候选致聋突变.

关键词:MARVELD2;非综合征耳聋(NSHL);单核苷酸多态性位点

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Adzhubei I, Jordan DM, Sunyaev SR, 2013. Predicting functional effect of human missense mutations using polyphen-2. Curr Protoc Hum Genet, 76(1):7.20.1-7.20.41.

[2]Babanejad M, Fattahi Z, Bazazzadegan N, et al., 2012. A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran. Am J Med Genet A, 158A(10):2485-2492.

[3]Chasman D, Adams RM, 2001. Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. J Mol Biol, 307(2):683-706.

[4]Chishti MS, Bhatti A, Tamim S, et al., 2008. Splice-site mutations in the TRIC gene underlie autosomal recessive nonsyndromic hearing impairment in Pakistani families. J Hum Genet, 53(2):101-105.

[5]Dror AA, Avraham KB, 2009. Hearing loss: mechanisms revealed by genetics and cell biology. Annu Rev Genet, 43:411-437.

[6]Dror AA, Avraham KB, 2010. Hearing impairment: a panoply of genes and functions. Neuron, 68(2):293-308.

[7]Higashi T, Lenz DR, Furuse M, et al., 2013. A “Tric” to tighten cell–cell junctions in the cochlea for hearing. J Clin Invest, 123(9):3712-3715.

[8]Kitajiri SI, Furuse M, Morita K, et al., 2004. Expression patterns of claudins, tight junction adhesion molecules, in the inner ear. Hear Res, 187(1-2):25-34.

[9]Krug SM, Amasheh S, Richter JF, et al., 2009. Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability. Mol Biol Cell, 20(16):3713-3724.

[10]Mašindová I, Šoltýsová A, Varga L, et al., 2015. MARVELD2 (DFNB49) mutations in the hearing impaired central European Roma population—prevalence, clinical impact and the common origin. PLoS ONE, 10(4):e0124232.

[11]Morton CC, Nance WE, 2006. Newborn hearing screening— a silent revolution. New Engl J Med, 354(20):2151-2164.

[12]Nayak G, Varga L, Trincot C, et al., 2015. Molecular genetics of MARVELD2 and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss. Hum Genet, 134(4):423-437.

[13]Ng PC, Henikoff S, 2003. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res, 31(13):3812-3814.

[14]Oda Y, Otani T, Ikenouchi J, et al., 2014. Tricellulin regulates junctional tension of epithelial cells at tricellular contacts through Cdc42. J Cell Sci, 127(Pt 19):4201-4212.

[15]Raleigh DR, Marchiando AM, Zhang Y, et al., 2010. Tight junction-associated marvel proteins MarvelD3, tricellulin, and occludin have distinct but overlapping functions. Mol Biol Cell, 21(7):1200-1213.

[16]Ramzan K, Shaikh RS, Ahmad J, et al., 2005. A new locus for nonsyndromic deafness DFNB49 maps to chromosome 5q12.3-q14.1. Hum Genet, 116(1-2):17-22.

[17]Riazuddin S, Ahmed ZM, Fanning AS, et al., 2006. Tricellulin is a tight-junction protein necessary for hearing. Am J Hum Genet, 79(6):1040-1051.

[18]Šafka Brožková D, Laštůvková J, Štěpánková H, et al., 2012. DFNB49 is an important cause of non-syndromic deafness in Czech Roma patients but not in the general Czech population. Clin Genet, 82(6):579-582.

[19]Schraders M, Ruiz-Palmero L, Kalay E, et al., 2012. Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment. Am J Hum Genet, 91(5):883-889.

[20]Smith RJH, Bale JF Jr, White KR, 2005. Sensorineural hearing loss in children. Lancet, 365(9462):879-890.

[21]Sterkers O, Ferrary E, Amiel C, 1988. Production of inner ear fluids. Physiol Rev, 68(4):1083-1128.

[22]Teng S, Michonova-Alexova E, Alexov E, 2008. Approaches and resources for prediction of the effects of non- synonymous single nucleotide polymorphism on protein function and interactions. Curr Pharm Biotechnol, 9(2):123-133.

[23]Wang Y, Virtanen J, Xue ZD, et al., 2017. I-TASSER-MR: automated molecular replacement for distant-homology proteins using iterative fragment assembly and progressive sequence truncation. Nucleic Acids Res, 45(W1):W429-W434.

[24]Yang JY, Zhang Y, 2015. I-TASSER server: new development for protein structure and function predictions. Nucleic Acids Res, 43(W1):W174-W181.

[25]Yang JY, Yan RX, Roy A, et al., 2015. The I-TASSER suite: protein structure and function prediction. Nat Methods, 12(1):7-8.

[26]Zheng J, Ying ZB, Cai ZY, et al., 2015. GJB2 mutation spectrum and genotype-phenotype correlation in 1067 Han Chinese subjects with non-syndromic hearing loss. PLoS ONE, 10(6):e0128691.

[27]List of electronic supplementary materials

[28]Table S1 Primers used in PCR

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE