Contribution of genetic variants to congenital heart defects in both singleton and twin fetuses: a Chinese cohort study.
Contribution of genetic variants to congenital heart defects in both singleton and twin fetuses: a Chinese cohort study.
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DOI：
10.1186/s13039-023-00664-y
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发表时间：
2024-01-04
影响因子：
1.3
通讯作者：
中科院分区：
文献类型：
--
作者：
遗传变异对先天性心脏病（CHD）的影响已在许多出生后队列中进行了研究，但在少数产前胎儿队列中进行了描述。总体而言，特定的遗传变异，特别是拷贝数变异（CNVs）导致CHD在不同的产前队列研究中有些不同。在这项研究中，共有1118个胎儿证实心脏病从三个单位超过5年的时间内，组成961单胎妊娠和157双胎妊娠。我们对所有病例进行染色体微阵列分析以检测染色体数目异常（NCAs）和致病性/可能致病性CNVs（P/LP CNVs），并对一些没有NCAs和P/LP CNVs的病例采用全外显子组测序以检测P/LP序列变异（P/LP SV）。总体而言，在17.6%（197/1118）的病例中发现了NCA和P/LP CNV，其中NCA占9.1%（102/1118），P/LP CNV占8.5%（95/1118）。非孤立性CHD组NCA的发生率显著高于单纯性CHD组（27.3%vs.4.4%，p < 0.001），但单纯性CHD组与非孤立性CHD组P/LP CNVs的发生率无显著差异（11.7%vs.7.7%）。在95个胎儿中共鉴定出109个P/LP CNVs，包括97个（89.0%）新生，6个（5.5%）父母遗传和6个（5.5%）父母信息不可用。16p11.2近端BP 4-BP 5缺失检出率为0.9%（10/1118），仅次于最常见的22q11.21近端A-D缺失（2.1%，23/1118）。大多数16p11.2缺失（8/10）检测是从头开始，并富集在冠心病病例与对照组相比，从以前的研究。此外，在12.9%（8/62）的无NCA和P/LP CNV的病例中发现SV，其中大多数为常染色体显性遗传的新发病例。我们的队列研究提供了单胎和双胎胎儿中遗传变异对CHD的贡献的深入概况; NCA和P/LP CNV分别占胎儿CHD的9.1%和8.5%。我们证实16p11.2缺失是CHD相关的热点CNV，频率仅次于22q11.21缺失。大多数检测到的16p11.2缺失是从头开始的。此外，在12.9%（8/62）无NCA或P/LP CNV的胎儿中鉴定出P/LP SV。在线版本包含补充材料，可通过10.1186/s13039-023-00664-y获得。
The contribution of genetic variants to congenital heart defects (CHDs) has been investigated in many postnatal cohorts but described in few prenatal fetus cohorts. Overall, specific genetic variants especially copy number variants (CNVs) leading to CHDs are somewhat diverse among different prenatal cohort studies. In this study, a total of 1118 fetuses with confirmed CHDs were recruited from three units over a 5-year period, composing 961 of singleton pregnancies and 157 of twin pregnancies. We performed chromosomal microarray analysis on all cases to detect numerical chromosomal abnormalities (NCAs) and pathogenic/likely pathogenic CNVs (P/LP CNVs) and employed whole-exome sequencing for some cases without NCAs and P/LP CNVs to detect P/LP sequence variants (P/LP SVs). Overall, NCAs and P/LP CNVs were identified in 17.6% (197/1118) of cases, with NCA accounting for 9.1% (102/1118) and P/LP CNV for 8.5% (95/1118). Nonisolated CHDs showed a significantly higher frequency of NCA than isolated CHD (27.3% vs. 4.4%, p < 0.001), but there was no significant difference in the frequency of P/LP CNVs between isolated and nonisolated CHD (11.7% vs. 7.7%). A total of 109 P/LP CNVs were identified in 95 fetuses, consisting of 97 (89.0%) de novo, 6 (5.5%) parental inherited and 6 (5.5%) with unavailable parental information. The 16p11.2 proximal BP4-BP5 deletion was detected in 0.9% (10/1118) of all cases, second only to the most common 22q11.21 proximal A-D deletion (2.1%, 23/1118). Most of the 16p11.2 deletions (8/10) detected were de novo, and were enriched in CHD cases compared with a control cohort from a previous study. Additionally, SV was identified in 12.9% (8/62) of cases without NCA and P/LP CNV, most of which were de novo with autosomal dominant inheritance. Our cohort study provides a deep profile of the contribution of genetic variants to CHDs in both singleton and twin fetuses; NCA and P/LP CNV contribute to 9.1% and 8.5% of CHD in fetuses, respectively. We confirmed the 16p11.2 deletion as a CHD-associated hotspot CNV, second only to the 22q11.21 deletion in frequency. Most 16p11.2 deletions detected were de novo. Additionally, P/LP SV was identified in 12.9% (8/62) of fetuses without NCA or P/LP CNV. The online version contains supplementary material available at 10.1186/s13039-023-00664-y.
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DOI：
10.1038/s41436-018-0266-3
发表时间：
2019-04
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Pizzo L;Jensen M;Polyak A;Rosenfeld JA;Mannik K;Krishnan A;McCready E;Pichon O;Le Caignec C;Van Dijck A;Pope K;Voorhoeve E;Yoon J;Stankiewicz P;Cheung SW;Pazuchanics D;Huber E;Kumar V;Kember RL;Mari F;Curró A;Castiglia L;Galesi O;Avola E;Mattina T;Fichera M;Mandarà L;Vincent M;Nizon M;Mercier S;Bénéteau C;Blesson S;Martin-Coignard D;Mosca-Boidron AL;Caberg JH;Bucan M;Zeesman S;Nowaczyk MJM;Lefebvre M;Faivre L;Callier P;Skinner C;Keren B;Perrine C;Prontera P;Marle N;Renieri A;Reymond A;Kooy RF;Isidor B;Schwartz C;Romano C;Sistermans E;Amor DJ;Andrieux J;Girirajan S
通讯作者：
Girirajan S
影响因子：
4
作者：
Chung, Wendy K.;Roberts, Timothy P. L.;Sherr, Elliott H.;Snyder, LeeAnne Green;Spiro, John E.
通讯作者：
Spiro, John E.
影响因子：
4
作者：
Ehrlich, Laurent;Prakash, Siddharth K.
通讯作者：
Prakash, Siddharth K.
影响因子：
0.7
作者：
Egbe A;Lee S;Ho D;Uppu S;Srivastava S
通讯作者：
Srivastava S
影响因子：
30.8
作者：
Jin SC;Homsy J;Zaidi S;Lu Q;Morton S;DePalma SR;Zeng X;Qi H;Chang W;Sierant MC;Hung WC;Haider S;Zhang J;Knight J;Bjornson RD;Castaldi C;Tikhonoa IR;Bilguvar K;Mane SM;Sanders SJ;Mital S;Russell MW;Gaynor JW;Deanfield J;Giardini A;Porter GA Jr;Srivastava D;Lo CW;Shen Y;Watkins WS;Yandell M;Yost HJ;Tristani-Firouzi M;Newburger JW;Roberts AE;Kim R;Zhao H;Kaltman JR;Goldmuntz E;Chung WK;Seidman JG;Gelb BD;Seidman CE;Lifton RP;Brueckner M
通讯作者：
Brueckner M