FISH联合染色体核型分析明确复发性流产家系遗传病因一例

doi:10.12280/gjszjk.20230409

摘要/Abstract

摘要：

自然流产病因复杂，包括胚胎因素、母体因素、环境因素和免疫功能异常等，约50%~60%的流产与胚胎染色体异常有关。报告1例因2次自然流产行夫妇外周血染色体核型分析和荧光原位杂交（fluorescence in situ hybridization，FISH）检测的情况。妻子染色体核型未见明显异常，丈夫染色体核型46,XY,t(1;11)(p36.2;q24)。丈夫携带的t(1;11)平衡易位可能是导致该家庭反复流产的原因。该案例验证了FISH检测对于可疑亚端粒结构重排的应用价值。

关键词: 流产, 习惯性, 核型分析, 原位杂交, 荧光, 分子诊断技术, 易位, 遗传

Abstract:

The etiology of spontaneous abortion is complex, including embryonic factors, maternal factors, environmental factors and abnormal immune function. Approximately 50%~60% abortions are related to fetal chromosomal abnormalities. We reported a case of twice spontaneous abortion. The couple were subject to both chromosome karyotype and fluorescence in situ hybridization (FISH) analysis. None of obvious abnormality was observed in the wife, while chromosome karyotype result showed 46,XY,t(1;11)(p36.2;q24) in the husband. The balanced translocation of t(1;11) carried by the husband may be the reason for recurrent spontaneous abortion in this family. The case indicated the application value of FISH technology in the verification of suspect subtelomeric rearrangements.

Key words: Abortion, habitual, Karyotyping, In situ hybridization, fluorescence, Molecular diagnostic techniques, Translocation, genetic

庄建龙, 江矞颖, 曾书红, 陈新英. FISH联合染色体核型分析明确复发性流产家系遗传病因一例[J]. 国际生殖健康/计划生育杂志, 2024, 43(3): 201-203.

ZHUANG Jian-long, JIANG Yu-ying, ZENG Shu-hong, CHEN Xin-ying. Genetic Analysis of A Family with Recurrent Spontaneous Abortion Using FISH Combined with Chromosome Karyotype[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(3): 201-203.

图/表 3

参考文献 25

[1]	Muttukrishna S, Jauniaux E, Greenwold N, et al. Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages[J]. Hum Reprod, 2002, 17(12):3072-3078. doi: 10.1093/humrep/17.12.3072. pmid: 12456605
[2]	van den Berg MM, van Maarle MC, van Wely M, et al. Genetics of early miscarriage[J]. Biochim Biophys Acta, 2012, 1822(12):1951-1959. doi: 10.1016/j.bbadis.2012.07.001. pmid: 22796359
[3]	Rai R, Regan L. Recurrent miscarriage[J]. Lancet, 2006, 368(9535):601-611. doi: 10.1016/S0140-6736(06)69204-0. pmid: 16905025
[4]	Allison JL, Schust DJ. Recurrent first trimester pregnancy loss: revised definitions and novel causes[J]. Curr Opin Endocrinol Diabetes Obes, 2009, 16(6):446-450. doi: 10.1097/MED.0b013e3283327fc5. pmid: 19779333
[5]	Meza-Espinoza JP, Anguiano LO, Rivera H. Chromosomal abnormalities in couples with reproductive disorders[J]. Gynecol Obstet Invest, 2008, 66(4):237-240. doi: 10.1159/000147170. pmid: 18645257
[6]	Neri G, Serra A, Campana M, et al. Reproductive risks for translocation carriers: cytogenetic study and analysis of pregnancy outcome in 58 families[J]. Am J Med Genet, 1983, 16(4):535-561. doi: 10.1002/ajmg.1320160412.
[7]	Shetty S, Nair J, Johnson J, et al. Preimplantation Genetic Testing for Couples with Balanced Chromosomal Rearrangements[J]. J Reprod Infertil, 2022, 23(3):213-223. doi: 10.18502/jri.v23i3.10013. pmid: 36415497
[8]	Zhang J, Zhang B, Liu T, et al. Partial trisomy 4q and monosomy 5p inherited from a maternal translocationt(4;5)(q33; p15) in three adverse pregnancies[J]. Mol Cytogenet, 2020, 13:26. doi: 10.1186/s13039-020-00492-4. pmid: 32625247
[9]	Codina-Pascual M, Navarro J, Oliver-Bonet M, et al. Behaviour of human heterochromatic regions during the synapsis of homologous chromosomes[J]. Hum Reprod, 2006, 21(6):1490-1497. doi: 10.1093/humrep/del028. pmid: 16484310
[10]	Blackwood DH, Fordyce A, Walker MT, et al. Schizophrenia and affective disorders--cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family[J]. Am J Hum Genet, 2001, 69(2):428-433. doi: 10.1086/321969. pmid: 11443544
[11]	Whalley HC, Dimitrova R, Sprooten E, et al. Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity[J]. PLoS One, 2015, 10(6):e0130900. doi: 10.1371/journal.pone.0130900.
[12]	He L, Carothers A, Blackwood DH, et al. Recombination patterns around the breakpoints of a balanced 1;11 autosomal translocation associated with major mental illness[J]. Psychiatr Genet, 1996, 6(4):201-208. doi: 10.1097/00041444-199624000-00006. pmid: 9149326
[13]	Quan Q, Li TJ, Ding XP, et al. Infertility caused by male partners with genetic defects in Sichuan Province of China[J]. Genet Mol Res, 2013, 12(4):6512-6520. doi: 10.4238/2013.December.11.2. pmid: 24390997
[14]	Paliwal P, Sharma A, Sahoo J, et al. An unusual association of hypospadias with partial deletion of chromosome 1q[J]. Fertil Steril, 2010, 93(7):2413.e11-e13. doi: 10.1016/j.fertnstert.2009.12.003.
[15]	Wang RX, Zhang HG, Pan Y, et al. Translocation breakpoints of chromosome 1 in male carriers: clinical features and implications for genetic counseling[J]. Genet Mol Res,2016 Oct 5;15(4). doi: 10.4238/gmr.15048707.
[16]	Chen YC, Huang XN, Kong CY, et al. Six families with balanced chromosome translocation associated with reproductive risks in Hainan Province: Case reports and review of the literature[J]. World J Clin Cases, 2020, 8(1):222-233. doi: 10.12998/wjcc.v8.i1.222.
[17]	Dong Z, Yan J, Xu F, et al. Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage[J]. Am J Hum Genet, 2019, 105(6):1102-1111. doi: 10.1016/j.ajhg.2019.10.003. pmid: 31679651
[18]	Madan K, Nieuwint AW, van Bever Y. Recombination in a balanced complex translocation of a mother leading to a balanced reciprocal translocation in the child. Review of 60 cases of balanced complex translocations[J]. Hum Genet, 1997, 99(6):806-815. doi: 10.1007/s004390050453. pmid: 9187678
[19]	Goldman AS, Hultén MA. Analysis of chiasma frequency and first meiotic segregation in a human male reciprocal translocation heterozygote, t(1;11)(p36.3;q13.1), using fluorescence in situ hybridisation[J]. Cytogenet Cell Genet, 1993, 63(1):16-23. doi: 10.1159/000133493. pmid: 8449032
[20]	Spriggs EL, Martin RH. Analysis of segregation in a human male reciprocal translocation carrier, t(1;11) (p36.3;q13.1), by two-colour fluorescence in situ hybridization[J]. Mol Reprod Dev, 1994, 38(3):247-250. doi: 10.1002/mrd.1080380303. pmid: 7917274
[21]	Battaglia A. Del 1p36 syndrome: a newly emerging clinical entity[J]. Brain Dev, 2005, 27(5):358-361. doi: 10.1016/j.braindev.2004.03.011.
[22]	Kang DS, Shin E, Yu J. 1p36 deletion syndrome confirmed by fluorescence in situ hybridization and array-comparative genomic hybridization analysis[J]. Korean J Pediatr, 2016, 59(Suppl 1):S14-S18. doi: 10.3345/kjp.2016.59.11.S14.
[23]	Heilstedt HA, Burgess DL, Anderson AE, et al. Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome[J]. Epilepsia, 2001, 42(9):1103-1111. doi: 10.1046/j.1528-1157.2001.08801.x. pmid: 11580756
[24]	Windpassinger C, Kroisel PM, Wagner K, et al. The human gamma-aminobutyric acid A receptor delta (GABRD) gene: molecular characterisation and tissue-specific expression[J]. Gene, 2002, 292(1/2):25-31. doi: 10.1016/s0378-1119(02)00649-2.
[25]	Pauta M, Grande M, Rodriguez-Revenga L, et al. Added value of chromosomal microarray analysis over karyotyping in early pregnancy loss: systematic review and meta-analysis[J]. Ultrasound Obstet Gynecol, 2018, 51(4):453-462. doi: 10.1002/uog.18929. pmid: 29055063