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

Abstract

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

CLC Number:

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.

Figures/Tables 2

Table 1

Indications and results of prenatal diagnosis and fetal follow-up in 22 cases of 1q21.1 microdelelions"

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

Table 1

Table 2

Indications and results of prenatal diagnosis and fetal follow-up in 17 cases of 1q21.1 duplications"

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

Table 2

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Prenatal diagnosis and genetic counseling of 1q21.1 microdeletion/ microduplication syndrome in 39 fetuses

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