Genetic Unit, Department of Pathology, Faculty of Medicine, University of Porto, Porto, Portugal.
I3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
Andrology. 2020 Mar;8(2):307-314. doi: 10.1111/andr.12686. Epub 2019 Jul 29.
Approximately 15% of couples worldwide are affected with infertility, attributed to a male co-factor in about half of the cases. Y chromosome microdeletions are the second most common genetic cause for male infertility, with a global prevalence of 2-10% in infertile men. Recently, CNV67, localized in X chromosome, has emerged as potential contributor to male infertility, with a described frequency of 1.1% in the oligo/azoospermic men.
To investigate the prevalence of Y-linked CNVs in a cohort of Portuguese infertile men and correlate the patients' phenotypes with a genetic alteration; to investigate the CNV67 deletion in a subset of patients and corroborate the role of this CNV in male infertility.
We retrospectively analysed a database of 4000 Portuguese infertile men for karyotype anomalies and Y microdeletions and selected a cohort of 400 for CNV67 screening analysis by quantitative PCR or single PCR plus/minus.
Karyotype anomalies were present in 263 patients (6.6%), with Klinefelter syndrome representing the most frequent karyotype anomaly (2.8%). Among the 4000 patients, the prevalence of Yq microdeletions was 4.6%. Ninety microdeletions (10.0%) were found in the azoospermic group, 44 deletions (4.5%) in the severe oligozoospermic group, 1 AZFc partial deletion (0.3%) in the mild-moderate oligozoospermic group and 2 partial AZFc deletions (0.4%) in the normozoospermic group. Complete AZFc deletions represented 56.8% of the Yq microdeletions. The CNV67 deletion frequency was 1.2% in the studied sample.
This study presents one of the largest samples of infertile men worldwide with the main purpose of correlating the Yq microdeletions with sperm count. Our findings are supported by previous reviews with large data and provide a reliable estimation of the prevalence of these anomalies in a Portuguese population. CNV67 was exclusively deleted in patients with spermatogenic impairment, showing a consistent genotype-phenotype correlation and a significant prevalence.
全球约有 15%的夫妇受到不孕不育的影响，其中约一半的病例与男性因素有关。Y 染色体微缺失是男性不育的第二大常见遗传原因，在不育男性中的全球患病率为 2-10%。最近，位于 X 染色体上的 CNV67 已成为男性不育的潜在致病因素，在少精/无精症男性中描述的频率为 1.1%。
调查葡萄牙不育男性队列中 Y 连锁 CNV 的患病率，并将患者表型与遗传改变相关联；调查亚组患者中 CNV67 的缺失情况，并证实该 CNV 在男性不育中的作用。
我们回顾性分析了 4000 名葡萄牙不育男性的核型异常和 Y 微缺失数据库，并选择了 400 名患者进行 CNV67 筛查分析，采用定量 PCR 或单 PCR 加/减。
263 名患者（6.6%）存在核型异常，其中 Klinefelter 综合征是最常见的核型异常（2.8%）。在 4000 名患者中，Yq 微缺失的患病率为 4.6%。在无精子症组中发现了 90 个微缺失（10.0%），在严重少精子症组中发现了 44 个缺失（4.5%），在轻度/中度少精子症组中发现了 1 个 AZFc 部分缺失（0.3%），在正常精子症组中发现了 2 个 AZFc 部分缺失（0.4%）。完全 AZFc 缺失占 Yq 微缺失的 56.8%。在研究样本中，CNV67 缺失频率为 1.2%。
本研究是全球最大的不育男性样本之一，主要目的是将 Yq 微缺失与精子计数相关联。我们的发现得到了具有大量数据的先前综述的支持，并为葡萄牙人群中这些异常的患病率提供了可靠的估计。CNV67 仅在有精子发生障碍的患者中缺失，显示出一致的基因型-表型相关性和显著的患病率。
