GJB2 Mutation Spectrum and Genotype-Phenotype Correlation in 1067 Han Chinese Subjects with Non-Syndromic Hearing Loss.
GJB2 Mutation Spectrum and Genotype-Phenotype Correlation in 1067 Han Chinese Subjects with Non-Syndromic Hearing Loss.
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1067 名中国汉族非综合征性听力损失受试者的 GJB2 突变谱和基因型-表型相关性
DOI：
10.1371/journal.pone.0128691
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Guan MX
中科院分区：
文献类型：
--
作者：
Zheng J;Ying Z;Cai Z;Sun D;He Z;Gao Y;Zhang T;Zhu Y;Chen Y;Guan MX
据报道，间隙连接β 2（GJB 2）突变是全球许多人群中非综合征性听力损失的主要原因。GJB 2变异体的谱和频率在不同的种族群体中差异很大，这些人群中的基因型仍然知之甚少。本研究对1067例中国汉族非综合征性耳聋患者的GJB 2基因进行了系统性和扩展性突变筛查，并对获得的GJB 2变异体进行了系统发育、结构和生物信息学分析。共发现25个GJB 2突变体（23个已知突变体和2个新突变体），包括6个移码突变、1个无义突变、16个错义突变和2个沉默突变。在该队列中，c.235delC是最常见的致病性突变。系统发育分析、结构分析和生物信息学分析表明，2个新变异体c.127G>T（p.V43L）、c.293G>C（p.R98P）和2个已知变异体c. 107 T>C（p.L36P）和c.187G>T（p.V63L）定位于高度保守的氨基酸。此外，这4种突变在203名健康个体中缺失，因此，它们可能是最有可能的候选致病突变。另外，共鉴定出66种基因型（24种新基因型和42种已知基因型），其中纯合子6种，复合杂合子20种，单杂合子18种，仅多态性的基因型21种，以及野生型基因型。其中致病突变纯合子153例（14.34%），复合杂合子63例（5.91%），单杂合子157例（14.71%）。同时携带两种致病性突变的病例中，有65.28%（141/216）表现为重度听力损失。这些数据表明，GJB 2基因突变负责约34.96%的中国东部浙江省汉族人群的非综合征性听力损失。此外，我们的研究结果也有力地支持了其他因素，如调节区的改变，额外的基因和环境因素可能有助于耳聋的临床表现。
Mutations in Gap Junction Beta 2 (GJB2) have been reported to be a major cause of non-syndromic hearing loss in many populations worldwide. The spectrums and frequencies of GJB2 variants vary substantially among different ethnic groups, and the genotypes among these populations remain poorly understood. In the present study, we carried out a systematic and extended mutational screening of GJB2 gene in 1067 Han Chinese subjects with non-syndromic hearing loss, and the resultant GJB2 variants were evaluated by phylogenetic, structural and bioinformatic analysis. A total of 25 (23 known and 2 novel) GJB2 variants were identified, including 6 frameshift mutations, 1 nonsense mutation, 16 missense mutations and 2 silent mutations. In this cohort, c.235delC is the most frequently observed pathogenic mutation. The phylogenetic, structural and bioinformatic analysis showed that 2 novel variants c.127G>T (p.V43L), c.293G>C (p.R98P) and 2 known variants c. 107T>C (p.L36P) and c.187G>T (p.V63L) are localized at highly conserved amino acids. In addition, these 4 mutations are absent in 203 healthy individuals, therefore, they are probably the most likely candidate pathogenic mutations. In addition, 66 (24 novel and 42 known) genotypes were identified, including 6 homozygotes, 20 compound heterozygotes, 18 single heterozygotes, 21 genotypes harboring only polymorphism(s) and the wild type genotype. Among these, 153 (14.34%) subjects were homozygous for pathogenic mutations, 63 (5.91%) were compound heterozygotes, and 157 (14.71%) carried single heterozygous mutation. Furthermore, 65.28% (141/216) of these cases with two pathogenic mutations exhibited profound hearing loss. These data suggested that mutations in GJB2 gene are responsible for approximately 34.96% of non-syndromic hearing loss in Han Chinese population from Zhejiang Province in eastern China. In addition, our results also strongly supported the idea that other factors such as alterations in regulatory regions, additional genes, and environmental factors may contribute to the clinical manifestation of deafness.
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影响因子：
1.7
作者：
Khandelwal, G.;Bhalla, S.;Panda, N. K.
通讯作者：
Panda, N. K.
影响因子：
4
作者：
RamShankar, M;Girirajan, S;Anand, A
通讯作者：
Anand, A
影响因子：
3.5
作者：
Han, Sung-Hee;Park, Hong-Joon;Lee, Kyoung-Ryul
通讯作者：
Lee, Kyoung-Ryul
DOI：
10.1073/pnas.0800831105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Ortolano, Saida;Di Pasquale, Giovanni;Chiorini, John A.
通讯作者：
Chiorini, John A.
影响因子：
6.1
作者：
Palmada, M;Schmalisch, K;Blin, N
通讯作者：
Blin, N