一例严重少弱精症患者的遗传学研究

摘要

目的 对1例严重少弱精症患者进行遗传学病因诊断.方法 应用染色体显带及荧光原位杂交(fluorescence in situ hybridization,FISH)检测,分析患者染色体畸变的来源及结构特征,并采用多重PCR技术对Y染色体无精子因子(azoospermia factor,AZF)进行微缺失检测.结果 患者G显带核型为45,X,der(15)(?∶∶p11.2 →qter) dn；双色FISH结果提示15号染色体短臂上的未知来源片段包含性别决定基因(sex-determing region of Y chromosome gene,SR Y),同时提示存在镶嵌型性染色体数目异常,结果描述为:nuc ish(DXZ1×1,SRY×1)[390]/ (DXZ1×2,SRY×1)[10];四色FISH结果提示15号衍生染色体为Y与15号染色体易位形成的假双着丝粒染色体,结果描述为:45,X,der(15)(?∶∶p11.2→qter) dn.ishpsudic(15;Y)(p11.2;q12) (D15Z1+,SNRPN+,PML+; SRY+,DYZ3+,DYZ1+). AZF微缺失的多重PCR检测结果显示AZFc部分缺失,缺失位点在sY254.结论 综合细胞与分子遗传学检测结果,该患者患不育症的遗传学病因为:Y与15号染色体易位形成的假双着丝粒染色体,以及AZFc部分缺失,影响正常的减数分裂过程而导致精子生成阻滞.%Objective To explore genetic etiologies of a patient with severe oligozoospermia and asthenozoospermia,Methods G-banded karyotyping and fluorescence in situ hybridization (FISH) were used to characterize the origin and structure of the abnormal chromosome discovered in this patient.Multiplex polymerase chain reaction (PCR) was used to detect microdeletion of azoospermia factor (AZF).Results G-banding revealed a karyotype of 45,X,der(15) (? ∶ ∶ p1 1.2→qter) dn for the patient.Dual-color FISH confirmed that SRY gene was present in a segment attached to the short arm of chromosome 15.Sex chromosome mosaicism and numerical abnormality therefore were both present.Dual-color FISH revealed karyotype of nuc ish (DXZ1× 1,SRY× 1) [390/400]/(DXZ1 × 2,SRY× 1) [10/400].Four-color FISH showed that the abnormal chromosome 15 has derived from a pseudodicentric (Y; 15) translocation,and that the breakpoint on Y chromosome was located at Yq12.G-banding and FISH results confirmed that the karyotypewas45,X,der(15)(? ∶∶p11.2→qter)dn.ish psu dic(15;Y)(p11.2;q12)(D15Z1+,SNRPN+,PML+;SRY+,DYZ3+,DYZ1 +).Microdeletion of AZFc combined with sY254 deletion was detected by multiplex PCR.Conclusion Cytogenetic and molecular genetic analysis of the patient has indicated meiotic disturbances with spermatogenetic arrest resulting from a pseudodicentric chromosome derived from Y; 15 translocation and spermatogenesis dysfunction resulting from partial deletion of AZFc region.