Clinical Application of Chromosome Microarray Analysis in Fetuses with Talipes Equinovarus

doi:10.12280/gjszjk.20220103

Abstract

Abstract:

Objective: To evaluate the clinical value of chromosome microarray analysis (CMA) in the fetuses with talipes equinovarus (TE). Methods: We retrospectively collected the clinic data of 157 cases of TE fetuses from January 2016 to July 2020 who were diagnosed by ultrasound and tested by CMA. The fetuses were then divided into two groups as the isolated TE group (107 cases) and the complex TE group (50 cases). The positive rate of chromosomal variations in each group was analyzed. The positive rates of clinically significant copy number variation (CNV) of the two groups were compared with the risk ratio of low-risk pregnancy cohorts, to analyze whether the risk was enriched in TE fetuses. Results: ①The total positive rate of clinically significant chromosomal variations of TE fetuses was 10.19% (16/157), the positive rate of chromosome aneuploidy was 5.73% (9/157), the positive rate of CNV was 6.37% (10/157), in which the positive rate of clinically significant CNV was 4.46% (7/157). There were no significant differences in the positive rate of clinically significant chromosomal variation, the positive rate of chromosome aneuploidy and the positive rate of clinically significant CNV between the two groups(P>0.05). ② The total positive rate of clinically significant CNV in the TE fetuses and the positive rate of clinically significant CNV in the isolated TE group were significantly higher than those in the low- risk pregnancy cohort, respectively (P<0.05). There was no significant difference in the positive rate of clinically significant CNV between the complex TE group and the low- risk pregnancy cohort (P>0.05). Conclusions: The risk of clinically significant CNV in the TE fetuses is significantly higher than that in the low-risk pregnancy population. CMA can improve the detection rate of CNV in the fetuses with TE by about 6% (10/157), while CMA has important clinical value in detecting chromosomal microdeletion/microduplication in the TE fetus.

Key words: Talipes equinovarus, Fetus, Chromosomes, DNA copy number variations, Aneuploidy, Prenatal diagnosis, Ultrasonography, Chromosome microarray analysis

LUO Xiao-hui, ZHOU Wei-ning, LI Yi, REN Cong-mian, HUANG Yan-lin, LU Jian. Clinical Application of Chromosome Microarray Analysis in Fetuses with Talipes Equinovarus[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(5): 365-369.

Figures/Tables 2

References 18

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序号	孕周	产前超声表现	染色体区段	片段大小（Mb）及变异类型	变异来源	已知综合征/ 涉及致病基因	妊娠结局
例1	23⁺	右侧TE,左侧脑室10 mm	22q11.2	3.25,缺失	-	22q11.2微缺失综合征	引产
例2	24⁺	双侧TE	22q11.2	2.88,缺失	-	22q11.2微缺失综合征	引产
例3	27	右侧TE	22q11.2	2.9,缺失	新发	22q11.2微缺失综合征	引产
例4	24⁺	双侧TE	16p13.11	1.5,缺失	新发	16p13.11微缺失综合征	顺产男婴3.3 kg,双侧TE,发育正常
例5	32⁺	双侧TE,双肾盂分离,羊水过多	Xp22.31	1.7,缺失	-	STS基因	引产
例6	20⁺	右侧TE,羊水过少	14q24.3-q32.33	29.9,重复	-	14q三体综合征	引产
例7	22⁺	双侧TE,羊水指数249 mm	5q31.1	2.7,缺失	母源	PITX1基因	剖宫产女婴2.5 kg,双侧TE,发育正常
例8	23	右侧TE胎儿、左侧侧脑室10 mm	19p13.3	1.44,缺失	-	MAP2K2基因	引产
例9	20⁺	双侧TE,双侧肾上腺回声增强	16p13.11	1.2,重复	-	与16p13.11微重复综合征部分重叠	顺产男婴3.0 kg,发育正常,双侧TE已治疗
例10	31⁺	双侧TE,双侧室管膜下高回声团,大小4 mm×4 mm、6 mm×4 mm,考虑出血;三尖瓣轻度返流	2p12	2.8,缺失	-	无	顺产女婴3.0 kg,发育正常,双侧TE已治疗

序号	孕周	产前超声表现	染色体区段	片段大小（Mb）及变异类型	变异来源	已知综合征/ 涉及致病基因	妊娠结局
例1	23⁺	右侧TE,左侧脑室10 mm	22q11.2	3.25,缺失	-	22q11.2微缺失综合征	引产
例2	24⁺	双侧TE	22q11.2	2.88,缺失	-	22q11.2微缺失综合征	引产
例3	27	右侧TE	22q11.2	2.9,缺失	新发	22q11.2微缺失综合征	引产
例4	24⁺	双侧TE	16p13.11	1.5,缺失	新发	16p13.11微缺失综合征	顺产男婴3.3 kg,双侧TE,发育正常
例5	32⁺	双侧TE,双肾盂分离,羊水过多	Xp22.31	1.7,缺失	-	STS基因	引产
例6	20⁺	右侧TE,羊水过少	14q24.3-q32.33	29.9,重复	-	14q三体综合征	引产
例7	22⁺	双侧TE,羊水指数249 mm	5q31.1	2.7,缺失	母源	PITX1基因	剖宫产女婴2.5 kg,双侧TE,发育正常
例8	23	右侧TE胎儿、左侧侧脑室10 mm	19p13.3	1.44,缺失	-	MAP2K2基因	引产
例9	20⁺	双侧TE,双侧肾上腺回声增强	16p13.11	1.2,重复	-	与16p13.11微重复综合征部分重叠	顺产男婴3.0 kg,发育正常,双侧TE已治疗
例10	31⁺	双侧TE,双侧室管膜下高回声团,大小4 mm×4 mm、6 mm×4 mm,考虑出血;三尖瓣轻度返流	2p12	2.8,缺失	-	无	顺产女婴3.0 kg,发育正常,双侧TE已治疗

组别	n	染色体非整倍体		有临床意义的CNV		有临床意义的染色体变异[例（%）]
组别	n	CMA结果（例）	阳性率[例（%）]	CMA结果（例）	阳性率[例（%）]	有临床意义的染色体变异[例（%）]
孤立性TE组	107	21-三体（2） XYY（2） XX/XXX（1）	5（4.67）	16p13.11微缺失综合征（1） 22q11.2微缺失综合征（3） 5q31.1区域缺失（1）	5（4.67）	10（9.34）
复杂性TE组	50	21-三体（1） 18-三体（2） 7-三体嵌合体（1）	4（8.00）	14q24.3-q32.3缺失（1） Xp22.31缺失（1）	2（4.00）	6（12.00）
χ²（P）		0.467*		1.000*		0.262（0.609）

组别	n	染色体非整倍体		有临床意义的CNV		有临床意义的染色体变异[例（%）]
组别	n	CMA结果（例）	阳性率[例（%）]	CMA结果（例）	阳性率[例（%）]	有临床意义的染色体变异[例（%）]
孤立性TE组	107	21-三体（2） XYY（2） XX/XXX（1）	5（4.67）	16p13.11微缺失综合征（1） 22q11.2微缺失综合征（3） 5q31.1区域缺失（1）	5（4.67）	10（9.34）
复杂性TE组	50	21-三体（1） 18-三体（2） 7-三体嵌合体（1）	4（8.00）	14q24.3-q32.3缺失（1） Xp22.31缺失（1）	2（4.00）	6（12.00）
χ²（P）		0.467*		1.000*		0.262（0.609）