1个Y染色体微缺失合并19号染色体臂间倒位的家系分析
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摘要
目的:对1个男性不育家系进行细胞和分子遗传学分析。方法:分析不育家系中3例男性的临床症状,并采用染色体核型分析、序列标签位点-PCR(STS-PCR)和多重连接依赖探针扩增(MLPA)等方法进行检测。结果:先证者及其哥哥的染色体核型为46,XY,inv(19)(p13.3q13.1),其父亲为46,XY;3例男性均为Y染色体AZFc区缺失携带者,MLPA检测发现三者在AZFb、AZFc区有相同的基因拷贝数的减少。结论:联合应用核型分析、Y染色体STS-PCR和MLPA等多种方法,揭示了1个男性不育家系的遗传学病因。
Objective: To investigate the familial cytomolecular genetics of an infertile male. Methods: We analyzed the clinical phenotypes and karyotypes of three males from the family of an infertile man, detected the sequence-tagged sites(STS) in the AZF deletions of the Y chromosome by multiplex polymerase chain reaction(PCR), and identified the target genes by multiplex ligation-dependent probe amplification(MLPA). Results: The karyotypes of the proband and his brother were 46, XY, inv(19)(p13.3 q13.1) and that of his father was 46, XY. The three males were all carriers of AZFc deletion of the Y chromosome, and all found with the same reduction of the gene copy number in the AZFb and AZFc regions. Conclusion: Combined use of karyotype analysis, Y chromosome STS PCR, and MLPA revealed the genetic causes of the male infertile family.
Objective: To investigate the familial cytomolecular genetics of an infertile male. Methods: We analyzed the clinical phenotypes and karyotypes of three males from the family of an infertile man, detected the sequence-tagged sites(STS) in the AZF deletions of the Y chromosome by multiplex polymerase chain reaction(PCR), and identified the target genes by multiplex ligation-dependent probe amplification(MLPA). Results: The karyotypes of the proband and his brother were 46, XY, inv(19)(p13.3 q13.1) and that of his father was 46, XY. The three males were all carriers of AZFc deletion of the Y chromosome, and all found with the same reduction of the gene copy number in the AZFb and AZFc regions. Conclusion: Combined use of karyotype analysis, Y chromosome STS PCR, and MLPA revealed the genetic causes of the male infertile family.
引文
[1] Dana M, Dumitru J, Veronica S. Chromosomal abnormality in men with impaired spermatogenesis. Int J Fertil Steril, 2014, 8(1): 35-42.
[2] Neto FT, Bach PV, Najari BB, et al. Genetics of male infertility. Curr Urol Rep, 2016, 17(10): 70.
[3] 罗小金, 魏凤香, 胡亮, 等. 产前胎儿染色体倒位的临床诊断分析. 实用医学, 2017, 33(13): 2183-2185.
[4] Dana M, Stoian V. Association of pericentric inversion of chromosome 9 and infertility in Romanian population. Maedica (Buchar), 2012, 7(1): 25-29.
[5] 赵书平, 张俊洁, 尤建, 等. 一种碘化钾提取外周血基因组DNA的方法. 中华医学遗传学杂志, 1999, 16(6): 395-396.
[6] Krausz C, Hoefsloot L, Simoni M, et al. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: State-of-the-art 2013. Andrology, 2014, 2(1): 5-19.
[7] Skaletsky H, Kuroda-Kawaguchi T, Minx P, et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature, 2003, 423(6942): 825-837.
[8] Zhang F, Li L, Wang L, et al. Clinical characteristics and treatment of azoospermia and severe oligospermia patients with Y-chromosome microdeletions. Mol Reprod Dev, 2013, 80(11): 908-915.
[9] Lu C, Jiang J, Zhang R, et al. Gene copy number alterations in the azoospermia-associated AZFc region and their effect on spermatogenic impairment. Mol Hum Reprod, 2014, 20(9): 836-843.
[10] Naasse Y, Charoute H, El Houate B, et al. Chromosomal abnormalities and Y chromosome microdeletions in infertile men from Morocco. BMC Urol, 2015, 15(1): 95.
[11] 罗小金, 魏凤香, 胡亮, 等. 孕中期胎儿染色体倒位的细胞遗传学分析. 中国优生与遗传杂志, 2017, 25(5): 61-62, 65.
[12] 郭东花, 任晨春, 梁玥宏, 等. 117例9号染色体倒位患者外周血染色体核型分析. 中国妇幼保健, 2017, 32(8): 1731-1734.
[13] Lopez-Exposito I, Guillen-Navarro E, Bafalliu JA, et al. Duplication 19q13-qter and deletion 19p13-pter arising from an inversion (19)(p13. 3q13. 3) of maternal origin. Eur J Med Genet, 2006, 49(6): 511-515.
[14] Fraser J, Ferrai C, Chiariello AM, et al. Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation. Mol Syst Biol, 2015, 11(12): 852.
[15] 韩金磊, 吴为人, 王凯. 染色体构象及其研究方法-3C技术. 分子植物育种, 2016, 14(12): 3501-3510.
[2] Neto FT, Bach PV, Najari BB, et al. Genetics of male infertility. Curr Urol Rep, 2016, 17(10): 70.
[3] 罗小金, 魏凤香, 胡亮, 等. 产前胎儿染色体倒位的临床诊断分析. 实用医学, 2017, 33(13): 2183-2185.
[4] Dana M, Stoian V. Association of pericentric inversion of chromosome 9 and infertility in Romanian population. Maedica (Buchar), 2012, 7(1): 25-29.
[5] 赵书平, 张俊洁, 尤建, 等. 一种碘化钾提取外周血基因组DNA的方法. 中华医学遗传学杂志, 1999, 16(6): 395-396.
[6] Krausz C, Hoefsloot L, Simoni M, et al. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: State-of-the-art 2013. Andrology, 2014, 2(1): 5-19.
[7] Skaletsky H, Kuroda-Kawaguchi T, Minx P, et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature, 2003, 423(6942): 825-837.
[8] Zhang F, Li L, Wang L, et al. Clinical characteristics and treatment of azoospermia and severe oligospermia patients with Y-chromosome microdeletions. Mol Reprod Dev, 2013, 80(11): 908-915.
[9] Lu C, Jiang J, Zhang R, et al. Gene copy number alterations in the azoospermia-associated AZFc region and their effect on spermatogenic impairment. Mol Hum Reprod, 2014, 20(9): 836-843.
[10] Naasse Y, Charoute H, El Houate B, et al. Chromosomal abnormalities and Y chromosome microdeletions in infertile men from Morocco. BMC Urol, 2015, 15(1): 95.
[11] 罗小金, 魏凤香, 胡亮, 等. 孕中期胎儿染色体倒位的细胞遗传学分析. 中国优生与遗传杂志, 2017, 25(5): 61-62, 65.
[12] 郭东花, 任晨春, 梁玥宏, 等. 117例9号染色体倒位患者外周血染色体核型分析. 中国妇幼保健, 2017, 32(8): 1731-1734.
[13] Lopez-Exposito I, Guillen-Navarro E, Bafalliu JA, et al. Duplication 19q13-qter and deletion 19p13-pter arising from an inversion (19)(p13. 3q13. 3) of maternal origin. Eur J Med Genet, 2006, 49(6): 511-515.
[14] Fraser J, Ferrai C, Chiariello AM, et al. Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation. Mol Syst Biol, 2015, 11(12): 852.
[15] 韩金磊, 吴为人, 王凯. 染色体构象及其研究方法-3C技术. 分子植物育种, 2016, 14(12): 3501-3510.