中文摘要：

目的报道1例Wolf-Hirschhorn综合征携带1条环状4号染色体合并严重少精子症的病例,并探讨精子发生障碍的可能机制。方法为检测患者初级精母细胞染色体的联会、重组和转录失活情况,用荧光标记联会复合体蛋白3（synaptonemal complex protein 3,SCP3）、错配修复基因蛋白（mut L homolog 1,MLH1）和乳腺癌易感基因1（breast cancer susceptibility gene 1,BRCA1）蛋白对睾丸活检样本进行免疫荧光染色。结果 SCP3染色显示对照组偶线期精母细胞占5.2%,而患者偶线期的精母细胞显著增高占35.4%,表明患者的生精阻滞在初级精母细胞的偶线期。MLH1染色显示每个细胞的结合位点数对照组为47.8±4.5,患者为45.9±5.9,后者明显减少（U=2.62,P〈0.05）。BRCA1染色显示患者所有粗线期细胞中都带有1条环状4号染色体,并有不同程度的不配对区域。结论环状4号染色体可能影响生殖细胞减数分裂Ⅰ期的进展,影响联会复合体的形成及未联会区域基因转录的活性,从而使精子的生成障碍,导致不育。

英文摘要：

Objective To report a case of Wolf-Hirschhorn syndrome with severe oligospermia carrying ring chromosome 5 and investi- gate the underlying mechanism of spermatogenetic failure in the patient. Methods Synaptonemal complex protein 3 （ SCP3 ）, mut L homolog 1 （ MLH1 ） and breast cancer susceptibility gene 1 （ BRCA1 ） in the testicular biopsy of the patients were examined by fluores- cence immunostaining to understand the synapsis, recombination and transcriptional inactivation of the chromosome in the primary sper- matocyte. Results SCP3 staining showed 35.4% of spermatocytes of the patient were in zygotene phase compared with 5.2% in controls, indicating spermatogenic arrest occurred at zygotene-pachytene stage. In MLH1 staining a significantly reduced recombination fre- quency with mean of（45.9 ± 5.9） MLH1 foci/cell was showed in comparison with （47.8 ± 4.5 ） of controls （ U = 2.62, P 〈 0.05 ）. BRCAlstaining showed the chromosome 4 in all pachytene cells displayed loop formation with varying degrees of unpaired regions. Conclusion The ring chromosome 4 may affect the progression of meiosisprophase Ⅰ , synapse formation, and transcriptional activation of asynapsed areas, leading to spermatogenic arrest and impair male fertility.