A common SLC26A4-linked haplotype underlying non-syndromic hearing loss with enlargement of the vestibular aqueduct
A common SLC26A4-linked haplotype underlying non-syndromic hearing loss with enlargement of the vestibular aqueduct
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DOI：
10.1136/jmedgenet-2017-104721
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发表时间：
2017-10-01
影响因子：
4
通讯作者：
Griffith, Andrew J.
中科院分区：
文献类型：
--
作者：
Chattaraj, Parna;Munjal, Tina;Griffith, Andrew J.
背景前庭导水管闭锁（伊娃）是儿童感音神经性耳聋最常见的影像学异常。在伊娃的白种人中经常检测到SLC26 A4基因编码区和剪接位点的突变。大约四分之一的伊娃患者有两个突变等位基因（M2），四分之一有一个突变等位基因（M1），一半没有突变等位基因（M0）。M2基因型与更严重的phenotype.Methods我们进行了基因型单体型分析和大规模平行测序的SLC26 A4区域的患者与M1伊娃及其family.Results我们确定了一个共享的新的单体型，称为CEVA（高加索伊娃），由12个罕见的变异上游的SLC26 A4。美国国立卫生研究院M1伊娃发现队列中10条“突变阴性”染色体中有7条和丹麦M1伊娃复制队列中6条突变阴性染色体中CEVA单倍型的存在高于观察到的1006条高加索对照染色体中28条的患病率（p
Background Enlargement of the vestibular aqueduct (EVA) is the most common radiological abnormality in children with sensorineural hearing loss. Mutations in coding regions and splice sites of the SLC26A4 gene are often detected in Caucasians with EVA. Approximately one-fourth of patients with EVA have two mutant alleles (M2), one-fourth have one mutant allele (M1) and one-half have no mutant alleles (M0). The M2 genotype is correlated with a more severe phenotype.Methods We performed genotype-haplotype analysis and massively parallel sequencing of the SLC26A4 region in patients with M1 EVA and their families.Results We identified a shared novel haplotype, termed CEVA (Caucasian EVA), composed of 12 uncommon variants upstream of SLC26A4. The presence of the CEVA haplotype on seven of ten 'mutation-negative' chromosomes in a National Institutes of Health M1 EVA discovery cohort and six of six mutation-negative chromosomes in a Danish M1 EVA replication cohort is higher than the observed prevalence of 28 of 1006 Caucasian control chromosomes (p