Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia
Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia
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DOI：
10.1136/jmedgenet-2013-102102
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发表时间：
2014-04-01
影响因子：
4
通讯作者：
Tolun, Aslihan
中科院分区：
文献类型：
--
作者：
Ayhan, Ozgecan;Balkan, Mahmut;Tolun, Aslihan
研究背景无精子症是指精液中缺乏可测量水平的精子。它影响了大约1%的男性，大多数特发性病例的遗传基础尚不清楚。我们调查了两个无血缘关系的特发性无精子症家系。家系1中有3个无精子症兄弟和1个少精子症兄弟;家系2中有3个无精子症兄弟。在家庭2的兄弟睾丸活检导致成熟逮捕的诊断在spermatoid stage.MethodsCandidate疾病位点，发现通过连锁映射使用单核苷酸多态性基因组扫描的数据。外显子组测序应用于寻找在locits.ResultsWe的变体在每个家庭和纯合截断突变p.R611X在TAF 4 B在家庭1和p.K507Sfs*3在ZMYND 15在家庭2中确定了两个候选位点。我们在45名无精子症和15名少精子症男性中没有检测到这些基因的任何突变。ZMYND 15的表达研究表明，最高的表达是在testis.ConclusionsBoth基因是已知的小鼠精子发生中的作用，但既没有在人类中进行了研究。据我们所知，他们是第一个基因确定隐性特发性男性生精障碍。假设造成单独无精子症的隐性基因在人和小鼠中一样多，那么每个基因可能只负责所有病例中的一小部分。
BackgroundAzoospermia is the absence of a measurable level of spermatozoa in the semen. It affects approximately 1% of all men, and the genetic basis of the majority of idiopathic cases is unknown. We investigated two unrelated consanguineous families with idiopathic azoospermia. In family 1, there were three azoospermic brothers and one oligozoospermic brother; and in family 2, there were three azoospermic brothers. Testis biopsy in the brothers in family 2 had led to the diagnosis of maturation arrest in the spermatid stage.MethodsCandidate disease loci were found via linkage mapping using data from single nucleotide polymorphism genome scans. Exome sequencing was applied to find the variants at the loci.ResultsWe identified two candidate loci in each family and homozygous truncating mutations p.R611X in TAF4B in family 1 and p.K507Sfs*3 in ZMYND15 in family 2. We did not detect any mutations in these genes in a cohort of 45 azoospermic and 15 oligozoospermic men. Expression studies for ZMYND15 showed that the highest expression was in the testis.ConclusionsBoth genes are known to have roles in spermatogenesis in mice but neither has been studied in humans. To our knowledge, they are the first genes identified for recessive idiopathic spermatogenic failure in men. Assuming that recessive genes for isolated azoospermia are as numerous in men as in mice, each gene is possibly responsible for only a small fraction of all cases.