PDF(Pubmed)
Abstract：
The molecular diagnosis of Y-chromosomal microdeletions is a common routine genetic test which is part of the diagnostic workup of azoospermic and severe oligozoospermic men. Since 1999, the European Academy of Andrology (EAA) and the European Molecular Genetics Quality Network (EMQN) have been actively involved in supporting the improvement of the quality of the diagnostic assays by publication of the laboratory guidelines for molecular diagnosis of Y-chromosomal microdeletions and by offering external quality assessment trials. The present revision of the 2004 laboratory guidelines summarizes all the clinical novelties related to the Y chromosome (classic, partial and gene-specific deletions, genotype-phenotype correlations, methodological issues) and provides an update on the results of the quality control programme. These aspects also reflect the consensus of a large group of specialists present at a round table session during the recent Florence-Utah-Symposium on \'Genetics of male infertility\' (Florence, 19-21 September, 2013). During the last 10 years the gr/gr deletion has been demonstrated as a significant risk factor for impaired sperm production. However, the screening for this deletion type in the routine diagnostic setting is still a debated issue among experts. The original basic protocol based on two multiplex polymerase chain reactions remains fully valid and appropriate for accurate diagnosis of complete AZF deletions and it requires only a minor modification in populations with a specific Y chromosome background. However, in light of novel data on genotype-phenotype correlations, the extension analysis for the AZFa and AZFb deletions is now routinely recommended. Novel methods and kits with excessively high number of markers do not improve the sensitivity of the test, may even complicate the interpretation of the results and are not recommended. Annual participation in an external quality control programme is strongly encouraged. The 12-year experience with the EMQN/EAA scheme has shown a steep decline in diagnostic (genotyping) error rate and a simultaneous improvement on reporting practice.
摘要：
Y染色体微缺失的分子诊断是一种常见的常规遗传测试，是无精子症和严重少精子症男性诊断检查的一部分。自1999年以来，欧洲男科科学院（EAA）和欧洲分子遗传学质量网络（EMQN）通过出版Y染色体微缺失的分子诊断实验室指南并通过提供外部质量评估试验，积极参与支持诊断测定质量的提高。2004年实验室指南的当前修订版总结了与Y染色体相关的所有临床新颖性（经典，部分和基因特异性缺失，基因型-表型相关性，方法问题)，并提供质量控制计划结果的最新信息。这些方面也反映了在最近的佛罗伦萨-犹他州-“男性不育症的遗传学”研讨会期间出席圆桌会议的一大批专家的共识（佛罗伦萨，9月19-21日,2013).在过去的10年中，gr/gr缺失已被证明是精子产生受损的重要风险因素。然而,在常规诊断环境中筛选这种缺失类型仍然是专家们争论的问题.基于两个多重聚合酶链反应的原始基本方案仍然完全有效，适合于准确诊断完整的AZF缺失，并且在具有特定Y染色体背景的人群中只需要进行少量修改。然而,根据基因型-表型相关性的新数据，现在常规建议对AZFa和AZFb缺失进行扩展分析.标记物数量过多的新方法和试剂盒不能提高测试的灵敏度，甚至可能使结果的解释复杂化，不建议这样做。强烈鼓励每年参加外部质量控制计划。EMQN/EAA计划的12年经验表明，诊断（基因分型）错误率急剧下降，同时报告实践也有所改善。
