Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and novel GJB2 variants.
Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and novel GJB2 variants.
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DOI：
10.1002/humu.9216
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发表时间：
2004-02-01
期刊：
影响因子：
3.9
通讯作者：
Meyer, Christian G
中科院分区：
文献类型：
--
作者：
Gasmelseed, Nagla M A;Schmidt, Martin;Meyer, Christian G
在许多人群中，很大一部分非综合征性常染色体隐性遗传性耳聋（NSARD）是由GJB 2基因的变异引起的。在这里，GJB 2变异体的频率分别在406和183名来自肯尼亚和苏丹的明显无关的儿童中进行了研究，这些儿童大多患有严重到极深的非综合征性耳聋。9名（2.2%）肯尼亚儿童和12名（6.6%）苏丹儿童是GJB 2基因编码序列内变异的携带者。在另外115个个体中检测到5 '邻近区域的变异。共识别出10个新的变异体，其中4个变异体位于GJB 2编码外显子2的相邻5 '区（g.3318- 6 T>A，g.3318- 15 C>T，g.3318- 34 C>T，g.3318- 35 T>G），6个碱基对缺失（g.3455_3460del [p.Asp46_Gln48delinsGlu]），导致终止密码子的变体（g.3512C>A [p.Tyr65X]）、同义变体（g.3395C>T [p.Thr26]、g.3503C>T [p.Asn62]、g.3627A>C [p.Arg104]）和一种非同义变体（g.3816C>A [p.Val167Met]）。此外，鉴定了先前描述的变体g.3352delG（通常命名为30 delG或35 delG）、g.3426G>A [p.Val37Ile]、g.3697G>A [p.Arg127His]、g.3774G>A [p.Val153Ile]和g.3795G>A [p.Gly160Ser]。除了g.3318- 34 C>T和g.3352delG之外，所有变体均异源发生。对于在肯尼亚和苏丹研究人群中发现的大多数变异，与NSARD的因果关系似乎不太可能。与许多其他种族相比，GJB 2编码区的遗传相关变体在苏丹和肯尼亚很少见，这表明其他遗传或表观遗传因素在这些国家中是耳聋的原因。
A large proportion of non-syndromic autosomal recessive deafness (NSARD) in many populations is caused by variants of the GJB2 gene. Here, the frequency of GJB2 variants was studied in 406 and 183 apparently unrelated children from Kenya and Sudan, respectively, with mostly severe to profound non-syndromic deafness. Nine (2.2 %) Kenyan and 12 (6.6 %) of the Sudanese children only were carriers of variants within the coding sequence of the GJB2 gene. Variants in the 5'-adjacent region were detected in further 115 individuals. A total of 10 novel variants was recognized, among them four variants in the adjacent 5'-region of the GJB2 coding exon 2 (g.3318-6T>A, g.3318-15C>T, g.3318-34C>T, g.3318-35T>G), a 6 base-pair deletion (g.3455_3460del [p.Asp46_Gln48delinsGlu]), a variant leading to a stop codon (g.3512C>A [p.Tyr65X]), synonymous variants (g.3395C>T [p.Thr26], g.3503C>T [p.Asn62], g.3627A>C [p.Arg104]), and one non-synonymous variant (g.3816C>A [p.Val167Met]). In addition, the previously described variants g.3352delG (commonly designated 30delG or 35 delG), g.3426G>A [p.Val37Ile], g.3697G>A [p.Arg127His], g.3774G>A [p.Val153Ile], and g.3795G>A [p.Gly160Ser] were identified. With the exception of g.3318-34C>T and g.3352delG, all variants occurred heterozygously. For most of the variants identified in the Kenyan and Sudanese study population, a causative association with NSARD appears to be unlikely. Compared to many other ethnic groups, deafness-associated variants of the coding region of GJB2 are rare in Sudan and Kenya, suggesting a role of other genetic, or epigenetic factors as a cause for deafness in these countries.