39例1q21.1微缺失/微重复综合征胎儿的产前诊断、遗传咨询及随访

doi:10.12372/jcp.2025.25e0085

摘要/Abstract

摘要：

目的探讨1q21.1微缺失/微重复综合征胎儿的临床表型、遗传咨询、妊娠结局及远期发育情况，构建该拷贝数变化胎儿全面的临床图景，为临床决策提供参考与依据。方法回顾性分析2017年1月至2022年12月，符合产前诊断指征并行羊水染色体核型分析和染色体拷贝数变异检测的孕妇资料。结果共纳入1q21.1微缺失/微重复综合征胎儿39例，检出率0.16%（39/24240）。拷贝数变异片段大小范围为0.24 Mb~62.34 Mb，其中22例（56.4%）为1q21.1微缺失，17例（43.6%）为1q21.1微重复。22例1q21.1微缺失胎儿中10例产前超声异常（10/22，45.6%），4例无创/血清学筛查高风险（4/22，18.2%），5例高龄（5/22，22.7%），3例有不良孕产史（3/22，13.6%）。缺失病例中6例行亲本溯源检测显示新发变异2例，父源性3例，母源性1例。17例1q21.1微重复胎儿中8例产前超声异常（8/17，45.6%），4例无创/血清学筛查高风险（5/17，29.4%），5例高龄（2/17，11.8%），3例有不良孕产史（3/17，17.6%）。重复病例中仅1例行亲代溯源检测显示为新发变异。结论 1q21.1微缺失/微重复在胎儿期的表现多样，CNV-seq技术对包括1q21.1在内的染色体微缺失/微重复综合征胎儿检出具有重要价值。

关键词: 1q21.1微缺失/微重复综合征, 染色体拷贝数变异检测, 亲代溯源, 遗传咨询

Abstract:

Objective To investigate the clinical phenotype, genetic counseling, pregnancy outcomes, and long-term developmental outcomes of fetuses with 1q21.1 microdeletion/ microduplication syndrome, and to provide a comprehensive clinical picture of fetuses with this copy number variation to inform clinical decision-making. Methods A retrospective analysis was conducted of pregnant women from January 2017 to December 2022. Results 39 cases of 1q21.1 microdeletion/microduplication syndrome fetuses were identified, with a detection rate of 0.16% (39/24,240). The size range of the copy number variation segments was 0.24 Mb to 62.34 Mb, with 22 cases (56.4%) being 1q21.1 microdeletions and 17 cases (43.6%) being 1q21.1 microduplications. Among the 22 cases of 1q21.1 microdeletion fetuses, 10 had prenatal ultrasound abnormalities (10/22, 45.6%), 4 had high-risk non-invasive/serological screening results (4/22, 18.2% ), 5 cases were of advanced maternal age (5/22, 22.7%), and 3 cases had a history of adverse pregnancy outcomes (3/22, 13.6%); among the deletion cases, 6 underwent parental origin testing, revealing 2 de novo mutations, 3 paternal origin, and 1 maternal. Among the 17 cases of 1q21.1 microduplication fetuses, 8 had prenatal ultrasound abnormalities (8/17, 45.6%), 4 had high-risk non-invasive/serological screening results (5/17, 29.4%), 5 were of advanced maternal age (2/17, 11.8%), and 3 had a history of adverse pregnancy outcomes (3/17, 17.6%); among the repeat cases, only 1 case showed a de novo mutation after parental lineage tracing. Conclusion 1q21.1 microdeletions/microduplications exhibit diverse manifestations during fetal development. CNV-seq technology holds significant value for detecting fetal cases of chromosomal microdeletion/microduplication syndromes, including 1q21.1.

Key words: 1q21.1 microdeletion/microduplication syndrome, chromosomal copy number variation testing, parental origin tracing, genetic counseling

中图分类号:

蔺朋武, 朱韶华, 赵中莹, 王静, 郝胜菊, 张庆华, 冯暄. 39例1q21.1微缺失/微重复综合征胎儿的产前诊断、遗传咨询及随访[J]. 临床儿科杂志, 2025, 43(8): 583-589.

LIN Pengwu, ZHU Shaohua, ZHAO Zhongying, WANG Jing, HAO Shengju, ZHANG Qinghua, FENG Xuan. Prenatal diagnosis and genetic counseling of 1q21.1 microdeletion/ microduplication syndrome in 39 fetuses[J]. Journal of Clinical Pediatrics, 2025, 43(8): 583-589.

图/表 2

表1

22例1q21.1微缺失病例的产前诊断指征与结果及胎儿生后随访情况"

序号	孕妇年龄 /岁	产前诊断指征	产前超声表现	CNV-seq结果	片段大小/Mb	CNV 评级	变异来源	随访情况/ 最终随访年龄
1	27	超声异常	三尖瓣反流，股骨长低于M-2SD线，肱骨长低于M-3SD线	seq[hg19]del(1)(q21.1q21.1) chr1:g.144000000_145740000del	1.74	VUS	新发	引产
2	41	超声异常	左心室强光点，羊水偏多，肝内强回声光斑	seq[hg19]del(1)(q21.1q21.2) chr1:g. 146720001_147440000 del	0.72	LP	/	失访
3	27	超声异常	单脐动脉，室间隔缺损	seq[hg19]del(1)(q21.1q21.2) chr1:g.144000000_147840000del	3.84	P	/	引产
4	37	超声异常	左肾实质回声略增强，并左肾内多发异常回声	seq[hg19]del(1)(q21.1q21.2) chr1:g.146500000_147840000del seq[hg19]dup(22)(q11.21) chr22:g.18960000_21480000dup	1.34； 2.52	P；P	/	引产
5	28	超声异常	右肾积水	seq[hg19]del(1)(q21.1q21.2) chr1:g.146500000_147840000del	1.34	P	/	失访
6	32	超声异常	室水平过膈血流，考虑室间隔缺损，束宽2.1mm	seq[hg19]del(1)(q21.1q21.2) chr1:g.146500000_147840000del	1.34	P	/	未见明显异常/随访至1岁5个月
7	26	超声异常	永久性右脐静脉，FL相当于25+周	seq[hg19]del(1)(q21.1q21.2) chr1:g.146560001_147840000del	1.28	P	/	引产
8	31	超声异常	NT：3.7mm	seq[hg19]del(1)(q21.1) chr1:g.145380000_145740000del seq[hg19]dup(8)(p23.1) chr8:g.10220001_11640000dup	0.36； 1.42	P VUS	/	耳廓畸形（反生）/随访至5岁5个月
9	32	超声异常	NT：3.2mm	seq[hg19]del(1)(q21.1) chr1:g.145440001_145700000del	0.26	VUS	/	引产
10	27	超声异常	NT：4.4mm	seq[hg19]del(1)(q21.1) chr1:g.145380000_145760000del	0.38	VUS	/	未见明显异常/随访至2岁7个月
11	26	T21 1:123	未见异常	seq[hg19]del(1)(q21.1q21.2) chr1:g.144860001_147440000del	2.58	P	/	失访
12	24	T18 1：244	未见异常	seq[hg19]del(1)(q21.1) chr1:g.145380001_145760000del	0.38	VUS	父源	未见明显异常/随访至4岁
13	24	T18 1：161	未见异常	seq[hg19]del(1)(q21.1) chr1:g.145380000_145760000del	0.38	LP	新发	引产
14	23	T21 1：85	未见异常	seq[hg19]del(1)(q21.1q21.2) chr1:g.146500001_147800000del seq[hg19]dup(11)(p11.2) chr11:g.48080001_48580000dup	1.3； 0.5	P VUS	父源	引产
15	36	高龄	未见异常	seq[hg19]del(1)(q21.1) chr1:g.145380000_145620000del	0.24	VUS	/	失访
16	37	高龄	未见异常	seq[hg19]del(1)(q21.1q21.2) chr1:g.146500001_147840000del	1.34	P	/	引产
17	36	高龄	未见异常	seq[hg19]del(1)(q21.1q21.2) chr1:g.146500001_147840000del	1.34	P	/	引产
18	37	高龄，高血压合并子痫前期	未见异常	seq[hg19]del(1)(q21.1q21.2) chr1:g.145720000_147840000del	2.12	P	/	引产
19	39	高龄	未见异常	seq[hg19]del(1)(q21.1q21.2) chr1:g.145740000_147840000del	2.1	P	/	引产
20	34	不良孕产史，1q21.1 杂合缺失生育史	未见异常	seq[hg19]del(1)(q21.1q21.1) chr1:g.145380000_145760000del	0.38	VUS	母源	未见明显异常/随访至2岁5个月
21	31	不良孕产史，唐筛开放性神经管畸形高风险	未见异常	seq[hg19]del(1)(q21.1q21.2) chr1:g.145720000_147840000del	2.12	P	父源	失访
22	24	不良孕产史，孕妇精神分裂症	未见异常	seq[hg19]del(1)(q21.1q21.2) chr1:g.146500000_147840000del	1.34	P	/	引产

表1

表2

17例1q21.1微重复病例的产前诊断指征与结果及胎儿生后随访情况"

病例序号	孕妇年龄 /岁	产前诊断指征	产前超声表现	CNV-seq结果	片段大小/Mb	CNV 评级	变异来源	随访情况/ 最终随访年龄
23	38	超声异常	肠管回声增强，高龄	seq[hg19]dup(1)(q21.1) chr1:g.145100000_145760000dup	0.66	VUS	/	失访
24	22	超声异常	左侧侧脑室正常高值，后颅窝池增宽，左侧肾盂分离	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146520001_147840000dup；seq[hg19]dup(22)(q11.21) chr22:g.18960000_21480000dup	1.32； 2.52	P P	/	引产
25	39	超声异常	右肾肾盂分离，高龄	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146520001_147840000dup	1.32	P	/	失访
26	29	超声异常	左侧脑室增宽，后颅窝池正常高值	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146500001_147840000dup	1.34	P	/	失访
27	28	超声异常	左心室强光点，后颅窝池增宽，羊水过多	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146520000_147780000dup	1.26	P	新发	引产
28	26	超声异常	可疑过膈血流，左心室强光点，双侧肾盂分离，三尖瓣少量反流	seq[hg19]dup(1)(q21.1q21.2) chr1:g.144000000_147840000dup	3.84	P	/	出生，未见明显异常/随访至1岁6个月
29	25	超声异常	双足内翻，动态观察后姿势不变	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146540000_147840000dup	1.30	P	/	引产
30	32	超声异常	胼胝体缺如；第三脑室增宽；双侧侧脑室正常高值	seq[hg19]dup(1)(q21.1q32.1)(mos) chr1:g.144000000_206340000dup	62.34	P	/	引产
31	37	超声异常	无创1q21.1-21.2处重复2.4Mb，左侧侧脑室正常高值	seq[hg19]dup(1)(q21.1q21.2) chr1:g.145380001_147840000dup seq[hg19]dup(11)(p11.2) chr11:g.48080001_48580000dup	2.46； 0.5	P VUS	/	出生，语言发育迟缓和社交互动障碍/随访至3岁8个月
32	27	T21 1：643；无创提示1q21.1-q21.2重复3.0Mb	未见异常	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146500001_147840000dup	1.34	P	/	出生，未见明显异常/随访至1岁7个月
33	34	T21 1：832；无创提示1q21.1-q21.2重复3.0Mb	未见异常	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146560000_147840000dup	1.28	P	/	引产
34	37	无创提示2号、5号和8号染色体偏多，高龄	未见异常	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146500000_147840000dup	1.34	P	/	引产
35	24	T21 1：27	未见异常	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146520000_147840000dup	1.32	P	/	出生，未见明显异常/随访至2岁5个月
36	37	高龄	未见异常	seq[hg19]dup(1)(q21.2) chr1:g.149040001_149460000dup	0.42	VUS	/	出生，未见明显异常/随访至5岁9个月
37	44	二代试管，高龄	未见异常	seq[hg19]dup(1)(q21.1q21.2) chr1:g.146540000_147400000dup	0.86	P	/	出生，未见明显异常/随访至1岁3个月
38	25	试管婴儿，男方Y染色体存在AZF C区缺失	未见异常	seq[hg19]dup(1)(q21.1q21.2) chr1:g.145740000_147840000dup	2.1	P	/	出生，未见明显异常/随访至2岁3个月
39	26	G3P2，二胎脑积水(脑瘫)，存活至今	未见异常	seq[hg19]dup(1)(q21.1q21.2) chr1:g.145020001_147800000dup	2.78	P	/	失访

表2

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