Likely damaging de novo variants in congenital diaphragmatic hernia patients are associated with worse clinical outcomes.
Likely damaging de novo variants in congenital diaphragmatic hernia patients are associated with worse clinical outcomes.
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先天性diaphragmatragmatic疝患者中可能损害从头变异的变体与临床结果较差有关。
DOI：
10.1038/s41436-020-0908-0
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Chung WK
中科院分区：
文献类型：
--
作者：
Qiao L;Wynn J;Yu L;Hernan R;Zhou X;Duron V;Aspelund G;Farkouh-Karoleski C;Zygumunt A;Krishnan US;Nees S;Khlevner J;Lim FY;Crombleholme T;Cusick R;Azarow K;Danko ME;Chung D;Warner BW;Mychaliska GB;Potoka D;Wagner AJ;Soffer S;Schindel D;McCulley DJ;Shen Y;Chung WK
先天性膈疝（CDH）与一些但并非所有个体的显著死亡率和长期发病率相关。我们假设导致CDH的单基因因素可能具有多效性，并与较差的临床结果相关。我们招募并前瞻性随访了647例新生儿CDH，并对462例三胞胎进行了基因组测序以确定新生变异。我们将病例分为具有和不具有可能的破坏性（LD）变异，并系统地评估遗传组之间CDH的临床结果。合并先天性异常的复杂病例死亡率高于单独病例（P=8×10−6）。LD变异的孤立病例死亡率与复杂病例相似，远高于无LD的孤立病例（P=3×10−3）。1个月时的趋势与肺动脉高压相似。与没有LD变异的病例相比，LD变异的病例在2年后的神经发育评估中估计得分低12-17分，这种差异在孤立病例和复杂病例中也相似。我们发现，与非LD变异相比，LD遗传变异与更高的死亡率、更严重的肺动脉高压和更差的神经发育结果相关。我们的研究结果对儿童CDH的预后、潜在干预和长期随访具有重要意义。
Congenital diaphragmatic hernia (CDH) is associated with significant mortality and long-term morbidity in some but not all individuals. We hypothesize monogenic factors that cause CDH are likely to have pleiotropic effects and be associated with worse clinical outcomes. We enrolled and prospectively followed 647 newborns with CDH and performed genomic sequencing on 462 trios to identify de novo variants. We grouped cases into those with and without likely damaging (LD) variants and systematically assessed CDH clinical outcomes between the genetic groups. Complex cases with additional congenital anomalies had higher mortality than isolated cases (P=8×10−6). Isolated cases with LD variants had similar mortality to complex cases and much higher mortality than isolated cases without LD (P=3×10−3). The trend was similar with pulmonary hypertension at 1 month. Cases with LD variants had an estimated 12–17 points lower scores on neurodevelopmental assessments at 2 years compared to cases without LD variants, and this difference is similar in isolated and complex cases. We found that the LD genetic variants are associated with higher mortality, worse pulmonary hypertension, and worse neurodevelopment outcomes compared to non-LD variants. Our results have important implications for prognosis, potential intervention and long-term follow up for children with CDH.
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影响因子：
3.5
作者：
Riggs ER;Church DM;Hanson K;Horner VL;Kaminsky EB;Kuhn RM;Wain KE;Williams ES;Aradhya S;Kearney HM;Ledbetter DH;South ST;Thorland EC;Martin CL
通讯作者：
Martin CL
DOI：
10.1183/16000617.0104-2017
发表时间：
2018-03-31
期刊：
European respiratory review : an official journal of the European Respiratory Society
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/j.jpeds.2012.12.036
发表时间：
2013-07-01
期刊：
The Journal of pediatrics
影响因子：
--
作者：
Wynn, Julia;Krishnan, Usha;Arkovitz, Marc S
通讯作者：
Arkovitz, Marc S
DOI：
10.1137/0907087
发表时间：
1986-10-01
期刊：
SIAM JOURNAL ON SCIENTIFIC AND STATISTICAL COMPUTING
影响因子：
--
作者：
SANTOSA, F;SYMES, WW
通讯作者：
SYMES, WW
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