Disorders of spermatogenesis: Perspectives for novel genetic diagnostics after 20 years of unchanged routine.
Disorders of spermatogenesis: Perspectives for novel genetic diagnostics after 20 years of unchanged routine.
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DOI：
10.1007/s11825-018-0181-7
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Röpke A
中科院分区：
文献类型：
--
作者：
Tüttelmann F;Ruckert C;Röpke A
不孕症是一种常见的疾病，估计影响10-15%的夫妇。临床原因可归因于男女伴侣各占一半。诊断男性不育主要依赖于精液（和激素）分析，其结果分为两种主要的表型少精症和无精症。临床常规分析在过去20年中没有变化，包括染色体畸变和Y染色体无精子因子缺失筛查。这些测试在大约4%的不育夫妇中的不育男性和20%的无精子症男性中建立了因果基因诊断。基因测序目前仅在非常罕见的低促性腺激素性腺功能减退症病例中进行，CFTR基因在阻塞性无精子症男性中进行常规分析。尽管如此，大量的基因已经被提出与男性不育有关，例如，敲除小鼠模型。特别是那些只在睾丸中表达的基因是进一步分析的潜在候选者。然而，迄今为止进行的全基因组分析（几个阵列CGH，六个GWAS和一些小外显子组测序研究）尚未导致改进的临床诊断测试。2017年，我们开始常规分析三个已验证的男性不育基因：NR 5A 1、DMRT 1和TEX 11。初步分析表明，这些基因中极有可能的致病性突变是4名男性无精子症的原因，相当于迄今为止分析的80名患者的5%，并将该组的诊断率提高到25%。在过去的几年里，我们观察到关于男性不育新候选基因的出版物急剧增加，特别是在无精子症男性中。此外，最近还作出了协调一致的努力，以在阐明男性不育的遗传原因方面取得进展，并在临床常规中引入新的检测策略。因此，我们相信，在不久的将来，关于男性不育遗传学的重大突破将实现，并将转化为临床常规，以改善患者/夫妇的护理。
Infertility is a common condition estimated to affect 10–15% of couples. The clinical causes are attributed in equal parts to the male and female partners. Diagnosing male infertility mostly relies on semen (and hormone) analysis, which results in classification into the two major phenotypes of oligo- and azoospermia. The clinical routine analyses have not changed over the last 20 years and comprise screening for chromosomal aberrations and Y‑chromosomal azoospermia factor deletions. These tests establish a causal genetic diagnosis in about 4% of unselected men in infertile couples and 20% of azoospermic men. Gene sequencing is currently only performed in very rare cases of hypogonadotropic hypogonadism and the CFTR gene is routinely analysed in men with obstructive azoospermia. Still, a large number of genes have been proposed to be associated with male infertility by, for example, knock-out mouse models. In particular, those that are exclusively expressed in the testes are potential candidates for further analyses. However, the genome-wide analyses (a few array-CGH, six GWAS, and some small exome sequencing studies) performed so far have not lead to improved clinical diagnostic testing. In 2017, we started to routinely analyse the three validated male infertility genes: NR5A1, DMRT1, and TEX11. Preliminary analyses demonstrated highly likely pathogenic mutations in these genes as a cause of azoospermia in 4 men, equalling 5% of the 80 patients analysed so far, and increasing the diagnostic yield in this group to 25%. Over the past few years, we have observed a steep increase in publications on novel candidate genes for male infertility, especially in men with azoospermia. In addition, concerted efforts to achieve progress in elucidating genetic causes of male infertility and to introduce novel testing strategies into clinical routine have been made recently. Thus, we are confident that major breakthroughs concerning the genetics of male infertility will be achieved in the near future and will translate into clinical routine to improve patient/couple care.
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影响因子：
4.5
作者：
Lima AC;Carvalho F;Gonçalves J;Fernandes S;Marques PI;Sousa M;Barros A;Seixas S;Amorim A;Conrad DF;Lopes AM
通讯作者：
Lopes AM
影响因子：
4.5
作者：
Krausz C;Hoefsloot L;Simoni M;Tüttelmann F;European Academy of Andrology;European Molecular Genetics Quality Network
通讯作者：
European Molecular Genetics Quality Network
影响因子：
5.8
作者：
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通讯作者：
O'Bryan, Moira K.
影响因子：
158.5
作者：
KAPLAN, E;SHWACHMA.H;HOLSCLAW, DS
通讯作者：
HOLSCLAW, DS
影响因子：
6.1
作者：
Chalmel, Frederic;Lardenois, Aurelie;Primig, Michael
通讯作者：
Primig, Michael