GJB2基因突变导致的遗传性耳聋
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摘要
缝隙连接蛋白的缺陷能引起缝隙连接通道功能障碍,从而导致综合征性耳聋及非综合征性耳聋。所有缝隙连接蛋白中,缝隙连接蛋白26(Connexin26,Cx26)异常的致病率最高,而该蛋白由GJB2(gap junctionprotein,beta-2)基因编码,GJB2基因突变后主要致病机理尚不明确,本文将对GJB2基因及其编码的缝隙连接蛋白26的结构和功能以及不同形式的GJB2基因突变引起的相关疾病进行综述。
The connexin defect can cause the dysfunction of gap connection channel, leading to syndromic and nonsyndromic hearing impairment. In all connexins, the morbidity of connexin 26 coded by gene is the highest. The main cause of GJB2 gene mutation is still unclear. The paper will talk about the same disease caused by GJB2 gene, the structure and function of connexin 26 and various GJB2 gene mutations.
The connexin defect can cause the dysfunction of gap connection channel, leading to syndromic and nonsyndromic hearing impairment. In all connexins, the morbidity of connexin 26 coded by gene is the highest. The main cause of GJB2 gene mutation is still unclear. The paper will talk about the same disease caused by GJB2 gene, the structure and function of connexin 26 and various GJB2 gene mutations.
引文
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[26]Koohiyan M,Hashemzadehchaleshtori M,Salehi M,et al.GJB2mutations causing autosomal recessive non-syndromic hearing loss(ARNSHL)in two Iranian populations:Report of two novel variants[J].International Journal of Pediatric Otorhinolaryngol ogy,2018,107:121-126.
[27]Minami SB,Mutai H,Nakano A,et al.GJB2-associated hearing loss undetected by hearing screening of newborns[J].Gene,2013,532(1):41-45.
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[29]Kecskeméti N,Sz?nyi M,Gáborján A,et al.Analysis of GJB2,mutations and the clinical manifestation in a large Hungarian cohort[J].European Archives of Oto-Rhino-Laryngology,2018,275(10):2441-2448.
[30]蔡超婵,黄莎莎,高雪,等.GJB2相关非综合征性感音神经性聋人工耳蜗植入后的疗效观察[J].临床耳鼻咽喉头颈外科杂志,2014,28(13):972-974.
[31]Abdurehim Y,Lehmann A,Zeitouni AG.Predictive Value of GJB2 Mutation Status for Hearing Outcomes of Pediatric Cochlear Implantation[J].Otolaryngology--head and neck surgery:official journal of American Academy of Otolaryngology-Head and Neck Surgery,2017,157(1):16-24
[32]Ahmad S,Tang W,Chang Q,et al.Restoration of connexin26protein level in the cochlea completely rescues hearing in a mouse model of human connexin30-linked deafness[J].Proc Natl Acad Sci USA,2007,104(4):1337-1341.
[2]Bilal S,Rashid H,Khattak JZK,et al.Structure modeling and mutational analysis of gap junction beta 2(GJB2)[J].African Journal of Biotechnology,2012,11(27):6965-6973.
[3]Mese G,Richard G,White TW.Gap junctions:basic structure and function[J].Invest Dermatol,2007,127(11):2516-2524.
[4]Martinez AD,Acuna R,Figueroa V,et al.Gap-junction channels dysfunction in deafness and hearing loss[J].Antioxid Redox Signal,2009,11(2):309-322.
[5]Liu W,Li H,Edin F,et al.Molecular composition and distribution of gap junctions in the sensory epithelium of the human cochlea-a super-resolution structured illumination microscopy(SR-SIM)study[J].Upsala Journal of Medical Sciences,2017,122(3):160-170.
[6]Snoeckx RL,Huygen PL,Feldmann D,et al.GJB2 Mutations and Degree of Hearing Loss:A Multicenter Study[J].American Journal of Human Genetics,2005,77(6):945-957.
[7]Beltramello M,Bicego M,Piazza V,et al.Permeability and gating properties of human connexins 26 and 30 expressed in HeLa cells[J].Biochem Biophys Res Commun,2003,305(4):1024-1033.
[8]Johnson SL,Ceriani F,Houston O,et al.Connexin-mediated signalling in non-sensory cells is crucial for the development of sensory inner hair cells in the mouse cochlea[J].Journal of Neuroscience,2017,37(2):258-268.
[9]Nickel R,Forge A.Gap junctions and connexins in the inner ear:their roles in homeostasis and deafness[J].Curr Opin Otolaryngol Head Neck Surg,2008,16(5):452-457.
[10]时晰,董燕粉,邱士伟,等.CX26第86位氨基酸多态性与遗传性聋相关性分析[J].中华耳科学杂志,2015,13(4):725-728.
[11]Mei L,Chen J,Zong L,et al.A deafness mechanism of digenic Cx26(GJB2)and Cx30(GJB6)mutations:Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall[J].Neurobiology of disease,2017,108:195-203.
[12]Zong L,Chen J,Zhu Y,et al.Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing[J].Biochemical&Biophysical Research Communications,2017,489(2):223-227.
[13]Dippold S,Butsch F,Schopf R,et al.Vohwinkel-Syndrom[J].HNO,2013,61(7):617-619.
[14]G?nül M,Gülü,Hizli P,et al.A family of Bart-Pumphrey syndrome[J].Indian J Dermatol Venereol Leprol,2012,78(2):178-181.
[15]Wang HH,Feng Y,Li HB,et al.Digenic mutations involving both the BSND,and GJB2,genes detected in Bartter syndrome type IV[J].International Journal of Pediatric Otorhinolaryngology,2017,92:17-20.
[16]杨铭华,李常兴,梅晓珍.一例进行性对称性红斑角化症GJB2基因突变分析[J].右江医学,2017,45(3):269-273.
[17]Burns FS.A case of generalized congenital erythroderma[J].Cutan Dis,1915,33:255-260.
[18]Bartenstein D,Chung HJ,Hussain S.Two Cases of Chronic Candidiasis in Keratitis-Ichthyosis-Deafness Syndrome[J].American Journal of Dermatopathology,2018,40(10):138-141.
[19]王森分,肖媛媛,徐哲等.角膜炎-鱼鳞病-耳聋综合征[J].临床皮肤科杂志,2016,45(3):177-179.
[20]Zheng J,Ying Z,Cai Z,et al.GJB2 Mutation Spectrum and Genotype-Phenotype Correlation in 1067 Han Chinese Subjects with Non-Syndromic Hearing Loss[J].Plos One,2015,10(6):e0128691.
[21]崔庆佳,王国建,张媛,等.GJB2、SLC26A4基因相关耳聋儿童的听力损失特点分析[J].听力学及言语疾病杂志,2014,22(2):120-123.
[22]代志瑶,孙宝春,黄莎莎,等.GJB2基因听力学表型与基因型关系分析[J].中华耳科学杂志,2014,12(1):34-36.
[23]Mahdieh N,Rabbani B.Statistical study of 35delG mutation of GJB2 gene:a meta-analysis of carrier frequency[J].Int JAudiol,2009,48(6):363-370.
[24]Gasparini P,Rabionet R,Barbujani G,et al.High carrier frequency of the 35delG deafness mutation in European populations[J].Eur J Hum Genet,2000,8(1):19-23.
[25]Lucotte G,Diéterlen F.The 35delG mutation in the connexin26 gene(GJB2)associated with congenital deafness:European carrier frequencies and evidence for its origin in ancient Greece[J].Genet Test,2005,9(1):20-25.
[26]Koohiyan M,Hashemzadehchaleshtori M,Salehi M,et al.GJB2mutations causing autosomal recessive non-syndromic hearing loss(ARNSHL)in two Iranian populations:Report of two novel variants[J].International Journal of Pediatric Otorhinolaryngol ogy,2018,107:121-126.
[27]Minami SB,Mutai H,Nakano A,et al.GJB2-associated hearing loss undetected by hearing screening of newborns[J].Gene,2013,532(1):41-45.
[28]王芳,陈小婉,徐百,等.2598例非综合征型耳聋患者基因型与临床表型的分析[J].中华耳科学杂志,2016,14(6):747-752.
[29]Kecskeméti N,Sz?nyi M,Gáborján A,et al.Analysis of GJB2,mutations and the clinical manifestation in a large Hungarian cohort[J].European Archives of Oto-Rhino-Laryngology,2018,275(10):2441-2448.
[30]蔡超婵,黄莎莎,高雪,等.GJB2相关非综合征性感音神经性聋人工耳蜗植入后的疗效观察[J].临床耳鼻咽喉头颈外科杂志,2014,28(13):972-974.
[31]Abdurehim Y,Lehmann A,Zeitouni AG.Predictive Value of GJB2 Mutation Status for Hearing Outcomes of Pediatric Cochlear Implantation[J].Otolaryngology--head and neck surgery:official journal of American Academy of Otolaryngology-Head and Neck Surgery,2017,157(1):16-24
[32]Ahmad S,Tang W,Chang Q,et al.Restoration of connexin26protein level in the cochlea completely rescues hearing in a mouse model of human connexin30-linked deafness[J].Proc Natl Acad Sci USA,2007,104(4):1337-1341.