Molecular and clinical characterization of Y chromosome microdeletions in infertile men: A 10-year experience in Italy
Molecular and clinical characterization of Y chromosome microdeletions in infertile men: A 10-year experience in Italy
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DOI：
10.1210/jc.2006-1981
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发表时间：
2007-03-01
影响因子：
5.8
通讯作者：
Foresta, Carlo
中科院分区：
文献类型：
--
作者：
Ferlin, Alberto;Arredi, Barbara;Foresta, Carlo
背景：在过去的几年里，男性不育患者对Y染色体长臂（Yq）微缺失检测的需求呈爆炸性增长。然而，尽管在该染色体的生物学方面取得了进展，但一些分子和临床问题并没有得到确切数据的支持。目的：目的是提供不育男性微缺失的类型和患病率、检测指征、基因型-表型相关性、精子非整倍性和遗传咨询等方面的信息。我们进行了一项前瞻性研究，从1996年1月至2005年12月在一个学术clinic.Patients：我们研究了3073连续不育男性，其中625人受到非梗阻性无精子症和1372人受到严重少精子症。99例微缺失患者进行了描述here.Main结果测量：Yq微缺失，精液分析，生殖激素，睾丸细胞学/组织学，和精子性染色体非整倍体被用作outcome measurements.Results：微缺失的患病率为3.2%，在男性不育的男性，8.3%的男性非梗阻性无精子症，和5.5%的男性严重少精子症。在精子数超过200万/ml的男性中，99个缺失中只有2个被发现。没有临床数据是有用的，以确定先验的患者具有较高的风险Yq微缺失。大多数缺失是AZFc-b2/b4亚型，并与可变的生精表型相关，72%的病例中存在精子。完全AZFa和AZFb（P5/近端P1）缺失分别与仅支持细胞综合征和精母细胞成熟改变相关，而这些区域的部分缺失与较温和的表型和频繁出现精子相关。男性与AZFc-b2/b4缺失产生较高比例的精子与性染色体和XY-二体性nullysomy的结论：这种广泛的临床研究扩大了知识的基因型-表型的关系，并证实，识别Yq微缺失具有显着的诊断和预后价值，增加了有用的信息，在这些患者的遗传咨询。
Context: An explosive growth in Y chromosome long arm (Yq) microdeletion testing demand for male infertility occurred in the past few years. However, despite the progresses in the biology of this chromosome, a number of molecular and clinical concerns are not supported by definitive data.Objective: The objective was to provide information on the type and prevalence of microdeletions in infertile males, indication for testing, genotype-phenotype correlation, sperm aneuploidies, and genetic counseling.Design and Setting: We performed a prospective study from January 1996 to December 2005 in an academic clinic.Patients: We studied 3073 consecutive infertile men, of which 625 were affected by nonobstructive azoospermia and 1372 were affected by severe oligozoospermia. Ninety-nine patients with microdeletions are described here.Main Outcome Measures: Yq microdeletions, seminal analysis, reproductive hormones, testicular cytology/histology, and sperm sex chromosomes aneuploidies were used as outcome measures.Results: The prevalence of microdeletions was 3.2% in unselected infertile men, 8.3% in men with nonobstructive azoospermia, and 5.5% in men with severe oligozoospermia. Only 2 of 99 deletions were found in men with more than 2 million sperm/ml. No clinical data are useful to identify a priori patients with higher risk of Yq microdeletions. Most deletions are of the AZFc-b2/b4 subtype and are associated with variable spermatogenic phenotype, with sperm present in 72% of the cases. Complete AZFa and AZFb (P5/Proximal P1) deletions are associated with Sertoli cell-only syndrome and alterations in spermatocyte maturation, respectively, whereas partial deletions in these regions are associated with milder phenotype and frequent presence of sperm. Men with AZFc-b2/b4 deletions produce a higher percentage of sperm with nullisomy for the sex chromosomes and XY-disomy.Conclusions: This extensive clinical research expands the knowledge on genotype-phenotype relationships and confirms that the identification of Yq microdeletions has significant diagnostic and prognostic value, adding useful information for genetic counseling in these patients.