Please wait a minute...
浙江大学学报(医学版)  2019, Vol. 48 Issue (4): 397-402    DOI: 10.3785/j.issn.1008-9292.2019.08.08
专题报道     
一例染色体复杂易位致胎儿多发畸形的遗传学诊断
罗玉琴(),沈敏,孙义锡,钱叶青,王丽雅,俞佳玲,胡珺洁,金帆,董旻岳*()
浙江大学医学院附属妇产科医院生殖遗传科 生殖遗传教育部重点实验室, 浙江 杭州 310006
Genetic analysis of a fetus with multiple malformations caused by complex translocations of four chromosomes
LUO Yuqin(),SHEN Min,SUN Yixi,QIAN Yeqing,WANG Liya,YU Jialing,HU Junjie,JIN Fan,DONG Minyue*()
Key Laboratory of Reproductive Genetics, Ministry of Education, Department of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
 全文: PDF(996 KB)   HTML( 11 )
摘要:

目的: 对一例染色体复杂易位致多发畸形胎儿进行遗传学分析和诊断。方法: 对一例多发畸形胎儿行G显带染色体核型分析、单核苷酸多态性微阵列(SNP array)及荧光原位杂交(FISH)检测。胎儿父母行外周血染色体核型分析及FISH检测。结果: 胎儿的羊水染色体核型为46,XN,t(12;13)(q22;q32)。SNP array显示胎儿存在1q42.13q44重复(20 192 kb)及15q26.1q26.3缺失(13 293 kb),核型分析与基因芯片结果不一致。FISH验证了SNP array的结果。母亲外周血FISH结果确认为隐匿性46,XX,t(1;15)(q42.1;q26.1)携带者,而胎儿遗传了其中一条衍生的15号染色体der(15)t(1;15)(q42.1;q26.1)。即胎儿遗传了父亲的t(12;13)(q22;q32)平衡易位及母亲的隐匿性平衡易位形成的衍生15号染色体。结论: 1q42.13q44重复和15q26.1q26.3缺失是导致本例胎儿畸形的遗传学病因,产前诊断时多种遗传学技术联合应用可为临床提供准确的诊断。

关键词: 胎儿/畸形染色体易位, 遗传多态性, 单核苷酸微阵列分析异常核型产前诊断原位杂交, 荧光    
Abstract:

Objective: To conduct genetic analysis in a fetus with complex translocation of four chromosomes. Methods: G-banded chromosome karyotype analysis, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed in a fetus with multiple malformations. Peripheral blood chromosome karyotype and FISH were also carried out for the parents. Results: The fetal amniotic fluid karyotype was 46, XY, t(12; 13)(q22; q32). SNP array analysis showed that there were 20 192 kb duplication at 1q42.13q44 and 13 293 kb deletion at 15q26.1q26.3 in the fetus. The results of karyotype and SNP array were inconsistent. FISH analyses on the parental peripheral blood samples demonstrated that the mother was a cryptic 46, XX, t(1; 15)(q42.1; q26.1) translocation. The fetus had inherited 46, XY, t(12; 13)(q22; q32) from his father and der(15)t(1; 15)(q42.1; q26.1) from his mother. Conclusions: The 1q42.13q44 duplication and 15q26.1q26.3 deletion may have contributed to the abnormal sonographic features of the fetus. The combination of cytogenetic, SNP array and FISH techniques was beneficial for providing an accurate genetic counseling.

Key words: Fetus/abnormalities    Chromosomes    Translocation, genetic    Polymorphism, single nucleotide    Microarray analysis    Abnormal karyotype    Prenatal diagnosis    In situ hybridization, fluorescence
收稿日期: 2019-03-28 出版日期: 2019-10-30
:  R349.3  
基金资助: 浙江省重点研发计划(2019C03025);浙江省医药卫生科技计划(2017KY427);浙江省教育厅科研项目(Y201737590)
通讯作者: 董旻岳     E-mail: luoyuqin@zju.edu.cn;dongmy@zju.edu.cn
作者简介: 罗玉琴(1977—), 女, 博士, 副主任技师, 主要从事生殖遗传学研究; E-mail: luoyuqin@zju.edu.cn; https://orcid.org/0000-0001-7839-110X
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  
罗玉琴
沈敏
孙义锡
钱叶青
王丽雅
俞佳玲
胡珺洁
金帆
董旻岳

引用本文:

罗玉琴,沈敏,孙义锡,钱叶青,王丽雅,俞佳玲,胡珺洁,金帆,董旻岳. 一例染色体复杂易位致胎儿多发畸形的遗传学诊断[J]. 浙江大学学报(医学版), 2019, 48(4): 397-402.

LUO Yuqin,SHEN Min,SUN Yixi,QIAN Yeqing,WANG Liya,YU Jialing,HU Junjie,JIN Fan,DONG Minyue. Genetic analysis of a fetus with multiple malformations caused by complex translocations of four chromosomes. J Zhejiang Univ (Med Sci), 2019, 48(4): 397-402.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.08.08        http://www.zjujournals.com/med/CN/Y2019/V48/I4/397

图 1  胎儿G显带染色体核型照片:46, XN, t(12;13)(q22;q32)
图 2  胎儿父亲显带染色体核型照片:46, XY, t(12;13)(q22;q32)
图 3  胎儿母亲显带染色体核型照片:46, XX
图 4  本例胎儿单核苷酸多态性微阵列检测结果
图 5  本例胎儿羊水及父母外周血中期分裂相荧光原位杂交分析结果
1 QIAN Y Q , FU X Y , WANG X Q et al. A feasible diagnostic approach for the translocation carrier from the indication of products of conception[J]. Mol Cytogenet, 2018, 11:12
doi: 10.1186/s13039-018-0362-8
2 QIAN Y Q , WANG X Q , CHEN M et al. Detection of fetal subchromosomal aberration with cell-free DNA screening led to diagnosis of parental translocation:Review of 11344 consecutive cases in a university hospital[J]. Eur J Med Genet, 2019, 62 (2): 115- 123
3 SHAFFER L G , BEJJANI B A . A cytogeneticist's perspective on genomic microarrays[J]. Hum Reprod Update, 2004, 10 (3): 221- 226
doi: 10.1093/humupd/dmh022
4 CHANTOT-BASTARAUD S , STRATMANN S , BRIOUDE F et al. Formation of upd(7)mat by trisomic rescue:SNP array typing provides new insights in chromosomal nondisjunction[J]. Mol Cytogenet, 2017, 10:28
doi: 10.1186/s13039-017-0329-1
5 FU F , DENG Q , LEI T Y et al. Clinical application of SNP array analysis in fetuses with ventricular septal defects and normal karyotypes[J]. Arch Gynecol Obstet, 2017, 296 (5): 929- 940
doi: 10.1007/s00404-017-4518-2
6 TRPCHEVSKA N , DIMOVA L , ARABADJI T et al. A family study of complex chromosome rearrangement involving chromosomes 1, 8, and 11 and its reproductive consequences[J]. J Assist Reprod Genet, 2017, 34 (5): 659- 669
doi: 10.1007/s10815-017-0893-7
7 WANG L Y , RAO X Q , LUO Y Q et al. Preimplantation genetic diagnosis and screening (PGD/S) using a semiconductor sequencing platform[J]. Hum Genomics, 2019, 13 (1): 1
8 MORRIS M L , BARONEZA J E , TEIXEEIRA P et al. Partial 1q duplications and associated phenotype[J]. Mol Syndromol, 2016, 6 (6): 297- 303
9 SHETH K , MOSS J , HYLAND S et al. The behavioral characteristics of Sotos syndrome[J]. Am J Med Genet A, 2015, 167A (12): 2945- 2956
10 WATANABE S , SHIMIZU K , OHASHI H et al. Detailed analysis of 26 cases of 1q partial duplication/triplication syndrome[J]. Am J Med Genet A, 2016, 170A (4): 908- 917
11 POOT M , VERRIJN STUART A A , VAN DAALEN E et al. Variable behavioural phenotypes of patients with monosomies of 15q26 and a review of 16 cases[J]. Eur J Med Genet, 2013, 56 (7): 346- 350
doi: 10.1016/j.ejmg.2013.04.001
[1] 张丹丹,王军梅. 胎儿肝血管瘤的产前影像学诊断和管理[J]. 浙江大学学报(医学版), 2019, 48(4): 439-445.
[2] 胡珺洁,钱叶青,孙义锡,俞佳玲,罗玉琴,董旻岳. 单核苷酸多态性微阵列分析对智力障碍和发育迟缓的遗传学诊断价值[J]. 浙江大学学报(医学版), 2019, 48(4): 420-428.
[3] 王雅芸,陈原,杨蒙蒙,习芳芳,占琪涛,蒋颖,赵柏惠,罗琼. 淋巴水囊瘤或颈部组织增厚胎儿预后分析[J]. 浙江大学学报(医学版), 2019, 48(4): 434-438.
[4] 雷雨,董旻岳. 孕妇年龄影响胎儿性染色体非整倍体风险[J]. 浙江大学学报(医学版), 2019, 48(4): 409-413.
[5] 殷一旋,朱晖,钱叶青,金晶磊,梅瑾,董旻岳. 2057名双胎妊娠孕妇无创产前筛查结果分析[J]. 浙江大学学报(医学版), 2019, 48(4): 403-408.
[6] 叶青,张莹莹,王晶晶,毛建华. Ⅳ型胶原α5链基因突变致奥尔波特综合征两家系遗传学分析[J]. 浙江大学学报(医学版), 2019, 48(4): 384-389.
[7] 许雨晴,钱叶青,姚维妙,董旻岳. Van der Woude综合征一家系遗传学分析[J]. 浙江大学学报(医学版), 2019, 48(4): 378-383.
[8] 梅瑾,刘姣,王敏,张闻,王昊,卢莎,何茶英,靳春雷. 八例22q11.2区微重复胎儿产前诊断和妊娠结局分析[J]. 浙江大学学报(医学版), 2019, 48(4): 429-433.
[9] 俞佳玲,孙义锡,胡珺洁,钱叶青,罗玉琴,董旻岳. 74例鼻骨缺失胎儿单核苷酸多态性微阵列检测结果分析[J]. 浙江大学学报(医学版), 2019, 48(4): 414-419.
[10] 刘蓓,杨艳梅,严恺,陈敏,王丽雅,黄颖之,钱叶青,董旻岳. Ⅰ型神经纤维瘤一家系的基因检测及产前诊断[J]. 浙江大学学报(医学版), 2019, 48(4): 367-372.
[11] 洪萍萍,郭冰洁,林莉,林细华,周嘉强. 葡萄糖激酶W257R突变致青少年发病的成人型糖尿病一家系分析[J]. 浙江大学学报(医学版), 2019, 48(2): 200-203.
[12] 田广烽,高慧,胡莎莎,舒强. 遗传和表观遗传机制在先天性心脏病中的研究进展[J]. 浙江大学学报(医学版), 2018, 47(3): 227-238.
[13] 李艳蝶 等. NLRP3炎症小体与儿童自身炎症性疾病研究进展[J]. 浙江大学学报(医学版), 2017, 46(4): 449-453.
[14] 洪芳 等. 浙江省新生儿有机酸尿症筛查及随访分析[J]. 浙江大学学报(医学版), 2017, 46(3): 240-247.
[15] 朱晖 等. 高龄孕妇外周血胎儿游离DNA产前筛查胎儿常见非整倍体的临床意义[J]. 浙江大学学报(医学版), 2017, 46(3): 256-261.