Sensorineural deafness and male infertility: a contiguous gene deletion syndrome
Sensorineural deafness and male infertility: a contiguous gene deletion syndrome
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DOI：
10.1136/jmg.2006.045765
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发表时间：
2007-04-01
影响因子：
4
通讯作者：
Smith, Richard J. H.
中科院分区：
文献类型：
--
作者：
Zhang, Yuzhou;Malekpour, Mahdi;Smith, Richard J. H.
背景：由连续基因缺失引起的综合征性听力损失并不常见。耳聋-不育综合征（DIS）是由15q15.3位点的大量连续基因缺失引起的。方法：对三个以耳聋和不孕为特征的新型综合征的家庭进行了描述。这三个家族没有共同的祖先，也没有相同的缺失。通过完成全基因组扫描建立连锁，并通过直接测序筛选连锁区域的候选基因。结果：缺失区域长约100 kb，涉及KIAA0377、CKMT1B、STRC和CATSPER2 4个基因，每个基因都有一个端粒重复。这种基因组结构是这些缺失发生的机制的基础。CATSPER2和STRC分别在精子和内耳中表达，与该缺失纯合的人的表型一致。据报道，在另一个分离男性不育和感音神经性耳聋的家族中也存在该区域的缺失，尽管也存在先天性促红细胞增生性贫血I型（CDAI），可能是由于另一个基因组区域的第二个缺失。结论：我们发现了三个分离常染色体隐性连续基因缺失综合征的家庭，其特征是耳聋和精子运动障碍。这种新的综合征是由15q15.3上的连续基因缺失引起的。
Background: Syndromic hearing loss that results from contiguous gene deletions is uncommon. Deafness-infertility syndrome (DIS) is caused by large contiguous gene deletions at 15q15.3.Methods: Three families with a novel syndrome characterised by deafness and infertility are described. These three families do not share a common ancestor and do not share identical deletions. Linkage was established by completing a genome-wide scan and candidate genes in the linked region were screened by direct sequencing.Results: The deleted region is about 100 kb long and involves four genes (KIAA0377, CKMT1B, STRC and CATSPER2), each of which has a telomeric duplicate. This genomic architecture underlies the mechanism by which these deletions occur. CATSPER2 and STRC are expressed in the sperm and inner ear, respectively, consistent with the phenotype in persons homozygous for this deletion. A deletion of this region has been reported in one other family segregating male infertility and sensorineural deafness, although congenital dyserythropoietic anaemia type I (CDAI) was also present, presumably due to a second deletion in another genomic region.Conclusion: We have identified three families segregating an autosomal recessive contiguous gene deletion syndrome characterised by deafness and sperm dysmotility. This new syndrome is caused by the deletion of contiguous genes at 15q15.3.