Du Yating, Huang Lihui, Cheng Xiaohua, Zhao Liping, Ruan Yu, Ni Tingting
Beijing Tongren Hospital, Capital Medical University.
Biosci Trends. 2016 Jul 19;10(3):220-6. doi: 10.5582/bst.2016.01096. Epub 2016 Jun 27.
The p.V37I (c.109G>A) mutation in the GJB2 gene is the common frequent cause of congenital deafness; however, its pathogenicity is debated. The present study investigated the prevalence of p.V37I in Chinese infants and young children and associated clinical characteristics. The subjects of the present study were screened for mutations in GJB2 (235delC, 299delAT, 176dell6, 35delG), SLC26A4 (IVS7-2A>G, 2168A>G), GJB3 (538C>T), and in the mitochondrial 12S rRNA gene (1555A>G, 1494C>T). Subjects with p.V37I underwent an audiological evaluation. GJB2 exon sequencing revealed that 20 subjects had p.V37I compound heterozygous mutations, one of whom had a family history; the mutations included c.235delC/p.V37I (n = 12), c.299AT/p.V37I (n = 7), and c.176del16/p.V37I (n = 1). Of the 20 subjects, 12 were referred for Universal Newborn Hearing Screening (UNHS). Nine of the 20 subjects had mild hearing loss in the better ear and 5 had moderate hearing loss in the better ear while 4 had normal hearing. Among subjects with the c.235delC/p.V37I mutation, 5 had mild hearing loss and 2 had moderate hearing loss while 3 had normal hearing. Among subjects with the c.299AT/p.V37I mutation, 3 had mld hearing loss and 3 had moderate hearing loss while 1 had normal hearing. One subject with the c.176del16/p.V37I mutation had mild hearing loss. Few studies have reported on the clinical characteristics of Chinese infants with p.V37I compound heterozygous mutations identified via screening for deafness genes and GJB2 sequencing. The c.235delC/p.V37I mutation was the most prevalent mutation found in subjects. The degree of hearing loss associated with p.V37I compound heterozygous mutations was mainly mild to moderate.
GJB2基因中的p.V37I（c.109G>A）突变是先天性耳聋的常见病因；然而，其致病性存在争议。本研究调查了中国婴幼儿中p.V37I的患病率及相关临床特征。本研究的受试者接受了GJB2（235delC、299delAT、176dell6、35delG）、SLC26A4（IVS7-2A>G、2168A>G）、GJB3（538C>T）以及线粒体12S rRNA基因（1555A>G、1494C>T）突变的筛查。携带p.V37I的受试者接受了听力学评估。GJB2外显子测序显示，20名受试者存在p.V37I复合杂合突变，其中1名有家族史；这些突变包括c.235delC/p.V37I（n = 12）、c.299AT/p.V37I（n = 7）和c.176del16/p.V37I（n = 1）。在这20名受试者中，12名是通过新生儿听力普遍筛查（UNHS）转诊而来的。20名受试者中，9名较好耳有轻度听力损失，5名较好耳有中度听力损失，4名听力正常。在携带c.235delC/p.V37I突变者中，5名有轻度听力损失，2名有中度听力损失，3名听力正常。在携带c.299AT/p.V37I突变者中，3名有轻度听力损失，3名有中度听力损失，1名听力正常。1名携带c.176del16/p.V37I突变者有轻度听力损失。很少有研究报道通过耳聋基因筛查和GJB2测序鉴定出的中国婴幼儿p.V37I复合杂合突变的临床特征。c.235delC/p.V37I突变是在受试者中发现的最常见突变。与p.V37I复合杂合突变相关的听力损失程度主要为轻度至中度。
