Genetics and Genomics of Pediatric Pulmonary Arterial Hypertension.
Genetics and Genomics of Pediatric Pulmonary Arterial Hypertension.
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DOI：
10.3390/genes11101213
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发表时间：
2020-10-16
期刊：
影响因子：
3.5
通讯作者：
Chung WK
中科院分区：
文献类型：
--
作者：
Welch CL;Chung WK
肺动脉高压（PAH）是一种罕见的疾病，尽管最近的治疗进展，死亡率高。这种疾病是由遗传和环境因素以及可能的基因-环境相互作用引起的。虽然PAH可在整个生命周期中表现出来，但儿科发病的疾病尤其具有挑战性，因为它通常与更严重的临床病程和合并症（包括肺/心脏发育异常）相关。鉴于这些差异，儿科发病PAH的遗传学研究中出现的数据表明遗传基础与成人不同可能并不奇怪。儿童的遗传负担更大，罕见遗传因素导致约42%的儿童发作PAH，而成人发作PAH约为12.5%。新发变异体通常与儿童PAH相关，至少占所有儿科病例的15%。儿童PAH患者的医疗护理标准基于成人数据的外推。然而，儿科发病PAH的病因异质性增加、预后较差和遗传负担增加，需要专门的儿科研究议程来改善分子诊断和临床管理。基因组学优先的方法将提高对儿科PAH及其与其他罕见儿科遗传性疾病相关性的理解。
Pulmonary arterial hypertension (PAH) is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors and likely gene–environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to ~42% of pediatric-onset PAH compared to ~12.5% of adult-onset PAH. De novo variants are frequently associated with PAH in children and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, increased etiologic heterogeneity, poorer prognosis, and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.
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影响因子：
2.1
作者：
Beghetti, Maurice;Rudzinski, Andrzej;Zhang, Min
通讯作者：
Zhang, Min
影响因子：
16.6
作者：
Gräf S;Haimel M;Bleda M;Hadinnapola C;Southgate L;Li W;Hodgson J;Liu B;Salmon RM;Southwood M;Machado RD;Martin JM;Treacy CM;Yates K;Daugherty LC;Shamardina O;Whitehorn D;Holden S;Aldred M;Bogaard HJ;Church C;Coghlan G;Condliffe R;Corris PA;Danesino C;Eyries M;Gall H;Ghio S;Ghofrani HA;Gibbs JSR;Girerd B;Houweling AC;Howard L;Humbert M;Kiely DG;Kovacs G;MacKenzie Ross RV;Moledina S;Montani D;Newnham M;Olschewski A;Olschewski H;Peacock AJ;Pepke-Zaba J;Prokopenko I;Rhodes CJ;Scelsi L;Seeger W;Soubrier F;Stein DF;Suntharalingam J;Swietlik EM;Toshner MR;van Heel DA;Vonk Noordegraaf A;Waisfisz Q;Wharton J;Wort SJ;Ouwehand WH;Soranzo N;Lawrie A;Upton PD;Wilkins MR;Trembath RC;Morrell NW
通讯作者：
Morrell NW
影响因子：
64.8
作者：
通讯作者：
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影响因子：
24.3
作者：
Galambos, Csaba;Mullen, Mary P.;Danhaive, Olivier
通讯作者：
Danhaive, Olivier
影响因子：
5.1
作者：
Bush, Douglas;Abman, Steven H.;Galambos, Csaba
通讯作者：
Galambos, Csaba