Update of the GJB2/DFNB1 mutation spectrum in Russia: a founder Ingush mutation del(GJB2-D13S175) is the most frequent among other large deletions.
Update of the GJB2/DFNB1 mutation spectrum in Russia: a founder Ingush mutation del(GJB2-D13S175) is the most frequent among other large deletions.
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DOI：
10.1038/jhg.2017.42
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发表时间：
2017-08
影响因子：
3.5
通讯作者：
Polyakov AV
中科院分区：
文献类型：
--
作者：
Bliznetz EA;Lalayants MR;Markova TG;Balanovsky OP;Balanovska EV;Skhalyakho RA;Pocheshkhova EA;Nikitina NV;Voronin SV;Kudryashova EK;Glotov OS;Polyakov AV
虽然GJB2基因序列的突变构成了导致常染色体隐性遗传性非综合征性耳聋的大多数变异，但很少有大的缺失被证明与DFNB1耳聋有关。目前，DFNB1听力损失的基因检测包括两种常见的大片段缺失：del(GJB6-D13S1830)和del(GJB6-D13S1854)的GJB2测序和DFNB1缺失分析。在这里，我们报告了最近发现的101 kb缺失del(GJB2-D13S175)在俄罗斯的频率、临床意义和进化起源。在1104例DFNB1基因双等位基因突变的多民族无关耳聋患者中，Del(GJB2-D13S175)等位基因频率高达0.5%(11/2208)，该等位基因主要与深度感音神经性耳聋相关。此外，在这项研究中还描述了8个以前未发表的GJB2突变。所有携带Del(GJB2-D13S175)的患者均为Ingush血统。在听力正常人群中，在印古什共和国发现Del(GJB2-D13S175)，携带率约为1%(2/241)。与缺失相关的单倍型分析显示，Ingushes人中有一个共同的创始人，缺失的年龄约为3000年。由于GJB2分析的标准方法遗漏了del(GJB2-D13S175)，我们在DFNB1听力损失的常规检测策略中加入了del(GJB2-D13S175)的检测。
Although mutations in the GJB2 gene sequence make up the majority of variants causing autosomal-recessive non-syndromic hearing loss, few large deletions have been shown to contribute to DFNB1 deafness. Currently, genetic testing for DFNB1 hearing loss includes GJB2 sequencing and DFNB1 deletion analysis for two common large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854). Here, we report frequency in Russia, clinical significance and evolutionary origins of a 101 kb deletion, del(GJB2-D13S175), recently identified by us. In multiethnic cohort of 1104 unrelated hearing loss patients with biallelic mutations at the DFNB1 locus, the del(GJB2-D13S175) allele frequency of up to 0.5% (11/2208) was determined and this allele was shown to be predominantly associated with profound sensorineural hearing loss. Additionally, eight previously unpublished GJB2 mutations were described in this study. All patients carrying del(GJB2-D13S175) were of the Ingush ancestry. Among normal hearing individuals, del(GJB2-D13S175) was observed in Russian Republic of Ingushetia with a carrier rate of ~1% (2/241). Analysis of haplotypes associated with the deletion revealed a common founder in the Ingushes, with age of the deletion being ~3000 years old. Since del(GJB2-D13S175) was missed by standard methods of GJB2 analysis, del(GJB2-D13S175) detection has been added to our routine testing strategy for DFNB1 hearing loss.
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