13号染色体重排所致严重少弱畸形精子症患者生精细胞减数分裂分析

Meiotic analysis of spermatogenic cells in severe oligoasthenoteratozoospermia with chromosome 13 rearrangement

目的:探讨13号染色体长臂相互缺失所致严重少弱畸形精子症患者生精阻滞的可能机制。方法:对1例13号染色体异常的严重少弱畸形精子症患者血液样本进行全基因组的寡核苷酸微阵列比较基因组杂交分析,以确定受累染色体的断裂点或基因缺失。对患者生殖细胞进行多色荧光原位杂交分析,以观察初级精母细胞13号染色体配对的情况。结果:寡核苷酸微阵列比较基因组杂交技术显示在13q12.3上有连续4个探针的缺失(A_16_P19757882,A_16_P02744617,A_14_P108858和A_16_P02744687),覆盖59.93 kb,位于基因FLT1和POMP之间,没有注释基因存在。初级精母细胞的减数分裂分析显示同源13号染色体配对错误,13q14和13qter信号彼此分离。结论:染色体重排导致的精子发生阻滞可能是由于生殖细胞第一次减数分裂同源染色体配对错误导致的。

Objective： To explore the possible mechanisms of spermatogenic arrest in severe oligoasthenoteratozoospermia in- duced by supernumerary, ring-neocentric 13q12. 3 ---~13q22 chromosome and reciprocal deletion. Methods： We performed a genomic-wide high-density oaCGH analysis for a case of oligoastbenoteratozoospermia with abnormal chromosome 13 to characterize the breakpoints of the chromosome involved or the gene deletion caused by the rearrangement. We also conducted a fluorescence in situ hy- bridization analysis on the germ cells using probes of 13q14/13qter to observe the pairing condition of homologous chromosome 13. Results： We identified by oaCGH analysis a microdeletion of 4 consecutive probes （ A 16_P19757882, A_16 P027d-4617, A 14 P108858 and A 16 P02744687 at chrl3ql2.3 ： 27979261 ---~28039191 ） with 59.93 kb between the FLT1 and POMP genes, with no annotated genes in the deleted region. The signals of 13q14 and 13qter were separated from each other in 90% of all the primary sper- matocytes examined, indicating the unpairing of homologous chromosome 13 or synapse failure. Conclusion ： Chromosomal rearrangement-induced spermatogenesis failure is caused by the unpairing of the homologous chromosomes involved in the first meiotic division of germ ceils.