Carrier frequency of GJB2 (connexin-26) mutations causing inherited deafness in the Korean population
Carrier frequency of GJB2 (connexin-26) mutations causing inherited deafness in the Korean population
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DOI：
10.1007/s10038-008-0342-7
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发表时间：
2008-12-01
影响因子：
3.5
通讯作者：
Lee, Kyoung-Ryul
中科院分区：
文献类型：
--
作者：
Han, Sung-Hee;Park, Hong-Joon;Lee, Kyoung-Ryul
GJB 2基因突变与遗传性听力损失有关。虽然大多数GJB 2突变的研究都涉及听力受损患者，但很少有关于这些突变在普通人群中发生频率的报道。本研究的目的是评估GJB 2基因突变导致遗传性耳聋在韩国普通人群中的患病率。从2，072名听力正常的新生儿中采集了血液样本。对干燥的血液样品进行PCR以扩增GJB 2基因的整个编码区，随后进行直接DNA测序。在GJB 2编码区共鉴定出24种不同的序列变异，包括8种致病性突变（p.V37I，p.G45E，p.R143 W，c.176_191del16，c.235delC，c.292_298dup7，c.299_300delAT和c.605ins46），四个多态性，（p.V27I、p.E114G、p.G160S和p.I203T）、六种未分类的变体（p.G4D、p.S85Y、p.T123N、p.R127H、p.A171T和p.F191L）和六种新变体（p.W3T、p.I20L、p.K41E、c.147C > T、c.186C > T和c.576A > G）。在听力正常的新生儿中，3%（62/2，072）发现了导致遗传性耳聋的致病性突变。在发现的8种致病突变中，p.V37I最常见（1.35%，28/2,072），其次是c.235delC（1.25%，26/2,072）。这些数据提供了有关GJB 2型听力损失的载波频率的信息，并对韩国人群遗传性耳聋的基因诊断检测具有重要意义。
Mutations in the GJB2 gene are associated with hereditary hearing loss. Although most studies of GJB2 mutations have dealt with hearing-impaired patients, there are few reports of the frequency of these mutations in the general population. The purpose of this study is to evaluate the prevalence of GJB2 mutations causing inherited deafness in the general Korean population. Blood samples were obtained from 2,072 newborns with normal hearing. The dried blood samples were subjected to PCR to amplify the entire coding region of the GJB2 gene, which was followed by direct DNA sequencing. A total of 24 different sequence variants were identified in the coding region of GJB2, including eight pathogenic mutations (p.V37I, p.G45E, p.R143 W, c.176_191del16, c.235delC, c.292_298dup7, c.299_300delAT and c.605ins46), four polymorphisms (p.V27I, p.E114G, p.G160S and p.I203T), six unclassified variants (p.G4D, p.S85Y, p.T123 N, p.R127H, p.A171T and p.F191L) and six novel variants (p.W3T, p.I20L, p.K41E, c.147C > T, c.186C > T and c.576A > G). Pathogenic mutations causing inherited deafness were identified in 3% (62/2,072) of the newborns with normal hearing. Of the eight pathogenic mutations found, p.V37I was the most common (1.35%, 28/2,072), followed by c.235delC (1.25%, 26/2,072). These data provide information about carrier frequency for GJB2-based hearing loss and have important implications for genetic diagnostic testing for inherited deafness in the Korean population.