四例男性不育患者的15q11额外小标记染色体分析

Analysis of small supernumerary marker chromosome 15qll in four infertile males

目的对4例男性不育患者所携带的额外小标记染色体（small supernumerary marker chromosome，sSMc）进行定位分析，以探讨其对男性不育的影响。方法综合应用外周血培养染色体核型G显带、N显带、多重连接依赖探针扩增（multiplex ligation dependent probe amplification，MLPA）、荧光原位杂交（fluorescence in situ hybridization，FISH）、单核苷酸多态性芯片（single nucleotide polymorphisms array，SNP—array）等技术对4例男性不育患者的15q11额外小标记染色体进行分析。结果G显带分析显示4例患者染色体核型均为47，XY，＋mar。N显带分析提示sSMC均为双随体，位于mar两侧。MI，PA（SALSA着丝粒探针p180／p182试剂盒）分析提示，1例患者的15q11．2基因拷贝数重复。SNP-array分析提示，4例患者均为15q11．1-q11．2区重复，片段大小分别为3．06Mb、0．9118Mb、1．728Mb、0．287Mb。CEP15D1524着丝粒探针FISH分析mar均有2个杂交信号，为双着丝粒染色体。综合分析4例患者mar均来自15号染色体，为双随体、双着丝粒，倒位重复形式，分子细胞核型为47，XY，＋mar．ishinvdup（15）（q11）（D1524＋＋）。结论15q11sSMC可能是导致男性不育的重要原因之一。

Objective To delineate the origins of small supernumerary marker chromosomes （sSMCs） identified in 4 infertile males. Methods The sSMCs were analyzed with combined G-banding, N-banding, multiplex ligation dependent probe amplification （MLPA）, fluorescence in situ hybridization （FISH） and single nucleotide polymorphisms array （SNP-array） techniques. Results Crbanding analysis has suggested a 46, X,- Y,＋mar karyotype in all of the 4 cases. N banding revealed that all of the sSMCs possessed two satellites located on both sides. By MLPA, 1 patient showed copy number gains for 15qll. 2 region. SNP- array analysis suggested that all had duplication for 15q11.1-qll. 2 region, spanning 3.06 Mb, 0. 9118 Mb, 1. 728 Mb and 0. 287 Mb, respectively. By FISH analysis, all of the sSMCs showed two hybridization signals, indicating that they were dicentric chromosomes. Conclusion In all of the four cases, the mar have derived from chromosome 15 and were bisatellited and dicentric, which give rise to a karyotype of 47,XY, ＋ish, inv dup（15）（qll）（D15Z4＋＋）, sSMC 15qll therefore may be a major cause for male infertility.