GJB2 and GJB6 Mutations in Non-Syndromic Childhood Hearing Impairment in Ghana
GJB2 and GJB6 Mutations in Non-Syndromic Childhood Hearing Impairment in Ghana
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DOI：
10.3389/fgene.2019.00841
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发表时间：
2019-09-18
影响因子：
3.7
通讯作者：
Wonkam, Ambroise
中科院分区：
文献类型：
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作者：
Adadey, Samuel M.;Manyisa, Noluthando;Wonkam, Ambroise
我们的研究旨在调查GJB2(间隙连接蛋白26)和GJB2(间隙连接蛋白30)突变与非综合征性儿童听力障碍(HI)相关，以及加纳环境因素对HI的影响。对1104名聋人学校学生的医疗报告进行了分析。招募了分离HI的家系，以及推测遗传起源的HI孤立病例。从外周血中提取DNA，然后对GJB2的整个编码区进行Sanger测序。采用多重聚合酶链式反应和Sanger测序法分析GJB2-D3S1830缺失的发生率。确定了97个分离HI的家庭，235个受影响的个人；从加纳的11所聋人学校总共抽取了166例假定遗传原因的孤立病例。环境因素，特别是脑膜炎，仍然是加纳HI损害的主要原因。男女比例为1.49。只有59.6%的患者在6~11岁进行了首次综合HI试验。几乎所有参与者都有感觉神经性HI(99.5%；n=639)。语前HI754例，占68.3%，其中先天性HI92.8%。家系分析提示96.9%的家族性病例为常染色体隐性遗传。在家族性病例中，GJB2-R143W突变在纯合子状态下占25.9%(21/81)，在非家族性非综合征先天性HI病例中占7.9%(11/140)。在没有HI的对照人群中，我们发现GJB2-R143W携带者的比例为1.4%(2/145)，处于杂合状态。在所有HI患者中均未发现GJB2-D3S1830缺失。GJB2-R143W突变占加纳家族性非综合征性HI的四分之一以上，应在临床实践中进行研究。大的连接蛋白30基因缺失(GJB2-D3S1830缺失)不是加纳先天性非综合征HI的原因。需要使用下一代测序方法和功能基因组学研究来确定加纳大多数家庭和孤立的HI病例中涉及的其他基因。
Our study aimed to investigate GJB2 (connexin 26) and GJB2 (connexin 30) mutations associated with non-syndromic childhood hearing impairment (HI) as well as the environmental causes of HI in Ghana. Medical reports of 1,104 students attending schools for the deaf were analyzed. Families segregating HI, as well as isolated cases of HI of putative genetic origin were recruited. DNA was extracted from peripheral blood followed by Sanger sequencing of the entire coding region of GJB2. Multiplex PCR and Sanger sequencing were used to analyze the prevalence of GJB2-D3S1830 deletion. Ninety-seven families segregating HI were identified, with 235 affected individuals; and a total of 166 isolated cases of putative genetic causes, were sampled from 11 schools for the deaf in Ghana. The environmental factors, particularly meningitis, remain a major cause of HI impairment in Ghana. The male/female ratio was 1.49. Only 59.6% of the patients had their first comprehensive HI test between 6 to 11 years of age. Nearly all the participants had sensorineural HI (99.5%; n = 639). The majority had pre-lingual HI (68.3%, n = 754), of which 92.8% were congenital. Pedigree analysis suggested autosomal recessive inheritance in 96.9% of the familial cases. GJB2-R143W mutation, previously reported as founder a mutation in Ghana accounted for 25.9% (21/81) in the homozygous state in familial cases, and in 7.9% (11/140) of non-familial non-syndromic congenital HI cases, of putative genetic origin. In a control population without HI, we found a prevalent of GJB2-R143W carriers of 1.4% (2/145), in the heterozygous state. No GJB2-D3S1830 deletion was identified in any of the HI patients. GJB2-R143W mutation accounted for over a quarter of familial non-syndromic HI in Ghana and should be investigated in clinical practice. The large connexin 30 gene deletion (GJB2-D3S1830 deletion) does not account for of congenital non-syndromic HI in Ghana. There is a need to employ Next Generation Sequencing approaches and functional genomics studies to identify the other genes involved in most families and isolated cases of HI in Ghana.