染色体22q11.2微重复的产前诊断及临床遗传学分析

doi:10.12280/gjszjk.20220351

摘要/Abstract

摘要：

目的：分析染色体22q11.2微重复胎儿的产前超声表型及遗传学分析。方法：回顾性分析2018年1月1日—2021年6月30日于泉州市妇幼保健院产前诊断中心行羊水或脐血染色体核型及单核苷酸多态性微阵列（single nucleotide polymorphism array，SNP-array）检测的13例22q11.2微重复胎儿的产前超声临床特征、遗传学病因及随访结果。结果：产前超声提示病例1存在先天性膈疝、胎儿颈后透明层厚度（nuchal translucency，NT）增厚和脉络丛囊肿；病例2及病例8彩色超声提示右锁骨下动脉迷走。SNP-array结果显示13例胎儿在22q11.2区段存在801.1 kb~3.8 Mb的重复片段。父母验证结果显示，2例遗传自表型正常的亲代，2例为新发变异。最终，10例胎儿继续妊娠，8例出生后随访未见明显异常，2例出生后失访。结论：产前染色体22q11.2微重复的临床意义判读需慎重，结合产前超声检查及亲代验证有助于妊娠结局的选择。

关键词: 多态性，单核苷酸, 染色体核型分析, 产前诊断, 染色体缺失, 染色体重复, DNA拷贝数变异, 22q11.2微重复

Abstract:

Objective: To analyze the prenatal ultrasonographic and genetic characteristics in fetuses with chromosome 22q11.2 microduplications. Methods: A total of 13 cases with 22q11.2 microduplications from Prenatal Diagnosis Center of Quanzhou Women′s and Children′s Hospital from January 1, 2018 to June 30, 2021 were included. Prenatal ultrasonographic characteristics, genetic causes and follow-up results were collected. Single nucleotide polymorphism array (SNP-array) and karyotype analysis were performed using amniotic fluid and umbilical cord blood. Results: The results of prenatal ultrasound demonstrated that case 1 had congenital diaphragmatic hernia and nuchal translucency (NT) thickening and choroid plexus cyst, and that case 2 and case 8 had the aberrant right subclavian artery. The results of SNP-array showed the microduplication fragments in 22q11.2 region range from 801.1 kb to 3.8 Mb in the enrolled 13 cases. Parental SNP-array verification indicated that two cases of microduplications were inherited from normal parents and that two of microduplications were de novo. At last, ten families chose to continue their pregnancies. Among them, 8 fetuses were followed up after birth without obvious abnormality, and 2 fetuses lost follow-up after birth. Conclusions: Interpretation of the clinical significance of prenatal 22q11.2 microduplications should be careful; the combination of prenatal ultrasonography and parental SNP-array verification will be helpful for the selection of pregnancy outcomes.

Key words: Polymorphism, single nucleotide, Chromosome karyotype analysis, Prenatal diagnosis, Chromosome deletion, Chromosome duplication, DNA copy number variations, 22q11.2 microduplications

李燕青, 苏景明, 陈耿波, 江矞颖, 王元白, 肖珊珊, 庄建龙. 染色体22q11.2微重复的产前诊断及临床遗传学分析[J]. 国际生殖健康/计划生育杂志, 2023, 42(1): 23-26.

LI Yan-qing, SU Jing-ming, CHEN Geng-bo, JIANG Yu-ying, WANG Yuan-bai, XIAO Shan-shan, ZHUANG Jian-long. Prenatal Diagnosis and Clinical Genetic Analysis of Chromosome 22q11.2 Microduplications[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(1): 23-26.

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病例	产前高危指征	SNP-array结果	片段大小	OMIM基因（个）	家系验证	妊娠结局
1	先天性膈疝，NT增厚，脉络丛囊肿	7p12.1(51,690,431-53,295,058)x3, 11q23.3q25(116,684,163-134,938,470)x3, 22q11.1q11.21(16,888,899-20,716,903)x3	3.8 Mb	43	母源t(11；22)	终止妊娠
2	DS 1/333，右锁骨下动脉迷走	22q11.21(18,648,855-21,951,650)x3	3.3 Mb	45	-	继续妊娠，生后失访
3	DS 1/57，心室强回声	22q11.21(18,648,855-21,800,471)x3	3.1 Mb	44	新发变异	终止妊娠
4	DS 1/242	22q11.21(18,648,855-21,464,764)x3	2.8 Mb	41	-	失访
5	DS 1/30	22q11.21(18,649,189-21,800,471)x3	3.1 Mb	44	-	继续妊娠，生后失访
6	DS 1/8，高龄孕妇，不良孕史	22q11.21(18,916,960-21,461,017)x3	2.5 Mb	39	-	继续妊娠，剖宫产一女婴
7	左侧脑室高值，部分肠道回声增强	22q11.21(18,916,960-21,029,657)x3	2.1 Mb	31	-	继续妊娠，剖宫产一男婴
8	右锁骨下动脉迷走	22q11.21(18,919,477-21,460,641)x3	2.5 Mb	39	-	继续妊娠，顺娩一女婴
9	单脐动脉，心室强回声	22q11.21(18,919,478-21,800,471)x3	2.8 Mb	47	遗传自父亲	继续妊娠，顺娩一男婴
10	DS 1/147	22q11.21(18,970,561-21,460,641)x3	2.4 Mb	38	遗传自母亲	继续妊娠，顺娩一女婴
11	心室强回声，肠道强回声	22q11.21(18,970,562-21,459,713)x3	2.4 Mb	42	-	继续妊娠，顺娩一男婴
12	DS 1/251，父亲Y染色体微缺失，辅助生殖受孕	22q11.21(20,980,874-21,804,597)x3	823.7 kb	11	-	继续妊娠，剖宫产一女婴
13	高龄孕妇，孕期不良药物接触史	22q11.21(20,999,334-21,800,471)x3	801.1kb	11	新发变异	继续妊娠，剖宫产一男婴

病例	产前高危指征	SNP-array结果	片段大小	OMIM基因（个）	家系验证	妊娠结局
1	先天性膈疝，NT增厚，脉络丛囊肿	7p12.1(51,690,431-53,295,058)x3, 11q23.3q25(116,684,163-134,938,470)x3, 22q11.1q11.21(16,888,899-20,716,903)x3	3.8 Mb	43	母源t(11；22)	终止妊娠
2	DS 1/333，右锁骨下动脉迷走	22q11.21(18,648,855-21,951,650)x3	3.3 Mb	45	-	继续妊娠，生后失访
3	DS 1/57，心室强回声	22q11.21(18,648,855-21,800,471)x3	3.1 Mb	44	新发变异	终止妊娠
4	DS 1/242	22q11.21(18,648,855-21,464,764)x3	2.8 Mb	41	-	失访
5	DS 1/30	22q11.21(18,649,189-21,800,471)x3	3.1 Mb	44	-	继续妊娠，生后失访
6	DS 1/8，高龄孕妇，不良孕史	22q11.21(18,916,960-21,461,017)x3	2.5 Mb	39	-	继续妊娠，剖宫产一女婴
7	左侧脑室高值，部分肠道回声增强	22q11.21(18,916,960-21,029,657)x3	2.1 Mb	31	-	继续妊娠，剖宫产一男婴
8	右锁骨下动脉迷走	22q11.21(18,919,477-21,460,641)x3	2.5 Mb	39	-	继续妊娠，顺娩一女婴
9	单脐动脉，心室强回声	22q11.21(18,919,478-21,800,471)x3	2.8 Mb	47	遗传自父亲	继续妊娠，顺娩一男婴
10	DS 1/147	22q11.21(18,970,561-21,460,641)x3	2.4 Mb	38	遗传自母亲	继续妊娠，顺娩一女婴
11	心室强回声，肠道强回声	22q11.21(18,970,562-21,459,713)x3	2.4 Mb	42	-	继续妊娠，顺娩一男婴
12	DS 1/251，父亲Y染色体微缺失，辅助生殖受孕	22q11.21(20,980,874-21,804,597)x3	823.7 kb	11	-	继续妊娠，剖宫产一女婴
13	高龄孕妇，孕期不良药物接触史	22q11.21(20,999,334-21,800,471)x3	801.1kb	11	新发变异	继续妊娠，剖宫产一男婴