罕见超数小标记染色体2例患者的分子细胞遗传学分析和辅助生殖指导  

Genetic analysis and assisted reproductive guidance for two infertile patients with rare small supernumerary marker chromosomes

作　　者：易朵 袁诗敏 胡亮 龚斐[1,2,3] 罗克莉 胡浩[1] 谭跃球 卢光琇 林戈 程德华 Yi Duo;Yuan Shimin;Hu Liang;Gong Fei;Luo Keli;Hu Hao;Tan Yueqiu;Lu Guangxiu;Lin Ge;Cheng Dehua(Reproductive and Genetic Hospital of Citic-Xiangya,Changsha,Hunan 410078,China;Institute of Reproduction and Stem Cell Engineering,Central South University,Changsha,Hunan 410078,China;National Engineering and Research Center of Human Stem Cells,Changsha,Hunan 410078,China)

机构地区：[1]长沙中信湘雅生殖与遗传专科医院,长沙410078 [2]长沙中南大学基础医学院生殖与干细胞工程研究所,长沙410078 [3]人类干细胞国家工程研究中心,长沙410078

出　　处：《中华医学遗传学杂志》2024年第5期519-525,共7页Chinese Journal of Medical Genetics

摘　　要：目的对2例罕见超数小标记染色体(sSMC)患者进行细胞分子水平的遗传学分析,为携带者夫妇的遗传咨询和生育指导提供借鉴。方法选取2018年10月31日和2021年5月10日于中信湘雅生殖与遗传专科医院进行生殖与遗传咨询的不孕不育患者2例为研究对象。应用常规G显带、荧光原位杂交(FISH)和基因组拷贝数变异测序(CNV-seq)确定sSMC的来源,应用显微切割结合高通量全基因组测序(MicroSeq)精准分析sSMC的常染色质片段大小和基因组信息。结果患者1的G显带和FISH结果提示其核型为mos 47,XY,del(16)(p10p12),+mar[65]/46,XY,del(16)(p10p12)[6]/48,XY,del(16)(p10p12),+2mar[3].ish mar(Tel 16p-,Tel 16q-,CEP 16-,WCP 16+),基因组CNV-seq结果为arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25],MicroSeq结果显示该sSMC来源于16p12.1p11.2(24979733-34023115 bp)。患者2的G显带和反向FISH结果提示其核型为mos 47,XX,+mar[37]/46,XX[23].rev ish CEN5,基因组CNV-seq结果为seq[GRCh37]dup(5)(p12q11.2)chr5:g(45120001_56000000)dup[0.8],MicroSeq结果显示该sSMC来源于5p12-q11.2(45132364-55967870 bp)。2对夫妇分别接受了植入前遗传学检测(PGT)和体外受精(IVF)助孕治疗。结论sSMC携带者的个性化分析对其后期的遗传咨询和生育指导具有重要意义,对于存在高遗传风险的sSMC携带者夫妇可考虑选择MicroSeq-PGT助孕。Objective To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes(sSMC).Methods Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31,2018 and May 10,2021,respectively were selected as the study subjects.The origin of sSMCs was determined by conventional G banding,fluorescence in situ hybridization(FISH)and copy number variation sequencing(CNV-seq).Microdissection combined with high-throughput whole genome sequencing(MicroSeq)was carried out to determine the fragment size and genomic information of their sSMCs.Results For patient 1,G-banded karyotyping and FISH revealed that he has a karyotype of mos47,XY,del(16)(p10p12),+mar[65]/46,XY,del(16)(p10p12)[6]/48,XY,del(16)(p10p12),+2mar[3].ish mar(Tel 16p-,Tel 16q-,CEP 16-,WCP 16+).CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25].MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115(GRCh37).For patient 2,karyotyping and reverse FISH revealed that she has a karyotype of mos 47,XX,+mar[37]/46,XX[23].rev ish CEN5,and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5:g(45120001_56000000)dup[0.8].MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37).After genetic counseling,both couples had opted in vitro fertilization(IVF)treatment and preimplantation genetic testing(PGT).Conclusion For individuals harboring sSMCs,it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance.Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing(MicroSeq-PGT)can provide an alternative treatment for carrier couples with a high genetic risk.

关 键 词：小超数标记染色体 荧光原位杂交 染色体显微切割 高通量全基因组测序 胚胎植入前遗传学检测 

分 类 号：R714.5[医药卫生—妇产科学] R394[医药卫生—临床医学]