Dinić Jelena, Kusić Jelena, Nikolić Aleksandra, Divac Aleksandra, Ristanović Momcilo, Radojković Dragica
Institute of Molecular Genetics and Genetic Engineering, Belgrade.
Vojnosanit Pregl. 2007 Apr;64(4):253-6. doi: 10.2298/vsp0704253d.
BACKGROUND/AIM: Impaired fertility of a male partner is the main cause of infertility in up to one half of all infertile couples. At the genetic level, male infertility can be caused by chromosome aberrations or gene mutations. The presence and types of Y chromosome microdeletions and cystic fybrosis transmembrane conductance regulator (CFTR) gene mutations as genetic cause of male infertility was tested in Serbian men. The aim of this study was to analyze CFTR gene mutations and Y chromosome microdelations as potential causes of male infertility in Serbian patients, as well as to test the hypothesis that CFTR mutations in infertile men are predominantly located in the several last exons of the gene.
This study has encompassed 33 men with oligo- or azoospermia. The screening for Y chromosome microdeletions in the azoospermia factor (AZF) region was performed by multiplex PCR analysis. The screening of the CFTR gene was performed by denaturing gradient gel electrophoresis (DGGE) method.
Deletions on Y chromosome were detected in four patients, predominantly in AZFc region (four of total six deletions). Mutations in the CFTR gene were detected on eight out of 66 analyzed chromosomes of infertile men. The most common mutation was F508del (six of total eight mutations).
This study confirmed that both Y chromosome microdeletions and CFTR gene mutations played important role in etiology of male infertility in Serbian infertile men. Genetic testing for Y chromosome microdeletions and CFTR gene mutations has been introduced in routine daignostics and offered to couples undergoing assisted reproduction techniques. Considering that both the type of Y chromosome microdeletion and the type of CFTR mutation have a prognostic value, it is recomended that AZF and CFTR genotyping should not only be performed in patients with reduced sperm quality before undergoing assisted reproduction, but also for the purpose of preimplantation and prenatal diagnostics in couples in which in vitro fertilization has been performed successfully.
背景/目的：男性伴侣生育能力受损是高达一半的不孕夫妇不孕的主要原因。在基因层面，男性不育可由染色体畸变或基因突变引起。本研究检测了塞尔维亚男性中作为男性不育遗传原因的Y染色体微缺失和囊性纤维化跨膜传导调节因子（CFTR）基因突变的存在情况及类型。本研究的目的是分析CFTR基因突变和Y染色体微缺失作为塞尔维亚患者男性不育的潜在原因，以及检验不育男性中CFTR突变主要位于该基因最后几个外显子的假说。
本研究纳入了33例少精子症或无精子症男性。通过多重PCR分析对无精子症因子（AZF）区域的Y染色体微缺失进行筛查。采用变性梯度凝胶电泳（DGGE）法对CFTR基因进行筛查。
在4例患者中检测到Y染色体缺失，主要位于AZFc区域（6例缺失中的4例）。在不育男性的66条分析染色体中，有8条检测到CFTR基因突变。最常见的突变是F508del（8例突变中的6例）。
本研究证实Y染色体微缺失和CFTR基因突变在塞尔维亚不育男性的男性不育病因中均起重要作用。Y染色体微缺失和CFTR基因突变的基因检测已被引入常规诊断，并提供给接受辅助生殖技术的夫妇。鉴于Y染色体微缺失类型和CFTR突变类型均具有预后价值，建议不仅对精子质量降低的患者在接受辅助生殖前进行AZF和CFTR基因分型，而且对于成功进行体外受精的夫妇，出于植入前和产前诊断的目的也应进行检测。
