A retrospective cohort analysis of the Yale pediatric genomics discovery program.
A retrospective cohort analysis of the Yale pediatric genomics discovery program.
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DOI：
10.1002/ajmg.a.62918
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发表时间：
2022-10
影响因子：
2
通讯作者：
Lakhani, Saquib A.
中科院分区：
文献类型：
--
作者：
Al-Ali, Samir;Jeffries, Lauren;Faustino, E. Vincent S.;Ji, Weizhen;Mis, Emily;Konstantino, Monica;Zerillo, Cynthia;Jiang, Yong-hui;Spencer-Manzon, Michele;Bale, Allen;Zhang, Hui;McGlynn, Julie;McGrath, James M.;Tremblay, Thierry;Brodsky, Nina N.;Lucas, Carrie L.;Pierce, Richard;Deniz, Engin;Khokha, Mustafa K.;Lakhani, Saquib A.
关键词：
耶鲁大学的儿科基因组学发现计划（PGDP）使用下一代测序（NGS）和转化研究来评估疑似患有罕见遗传疾病的具有广泛表型的复杂患者。我们对2015年6月至2020年7月期间评估的356名PGDP先证者进行了回顾性队列分析，查询了我们的数据库，包括参与者人口统计学，临床特征，NGS结果以及诊断和研究结果。整个研究队列（n=356）中最常见的三种表型为免疫系统异常（n=105，29%）、综合征或多系统疾病（n=103，29%）和心血管系统异常（n=62，17%）。在最终分类的216例患者中，77例（36%）获得新诊断，139例（64%）未确诊;其余140例患者仍在积极研究中。在67例（89%）中发现了单基因诊断;最大的一组在已知的疾病基因中有变异，但有新的贡献，如新的变异（n=31，40%）或扩展的表型（n=14，18%）。最后，5例PGDP诊断（8%）提示新的基因-表型关系。广泛的患者可以从结合NGS和功能分子分析的单一受试者研究中受益。所有儿科医生都应该考虑对缺乏精确分子诊断的患者进行进一步的遗传学评估。
The Pediatric Genomics Discovery Program (PGDP) at Yale uses next generation sequencing (NGS) and translational research to evaluate complex patients with a wide range of phenotypes suspected to have rare genetic diseases. We conducted a retrospective cohort analysis of 356 PGDP probands evaluated between June 2015 and July 2020, querying our database for participant demographics, clinical characteristics, NGS results, and diagnostic and research findings. The three most common phenotypes amongst the entire studied cohort (n=356) were immune system abnormalities (n=105, 29%), syndromic or multisystem disease (n=103, 29%), and cardiovascular system abnormalities (n=62, 17%). Of 216 patients with final classifications, 77 (36%) received new diagnoses and 139 (64%) were undiagnosed; the remaining 140 patients were still actively being investigated. Monogenetic diagnoses were found in 67 (89%); the largest group had variants in known disease genes but with new contributions such as novel variants (n=31, 40%) or expanded phenotypes (n=14, 18%). Finally, five PGDP diagnoses (8%) were suggestive of novel gene-to-phenotype relationships. A broad range of patients can benefit from single subject studies combining NGS and functional molecular analyses. All pediatric providers should consider further genetics evaluations for patients lacking precise molecular diagnoses.
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影响因子：
4
作者：
Marquez J;Mann N;Arana K;Deniz E;Ji W;Konstantino M;Mis EK;Deshpande C;Jeffries L;McGlynn J;Hugo H;Widmeier E;Konrad M;Tasic V;Morotti R;Baptista J;Ellard S;Lakhani SA;Hildebrandt F;Khokha MK
通讯作者：
Khokha MK
影响因子：
26.1
作者：
Berry, Jay G.;Hall, Matt;Hall, David E.;Kuo, Dennis Z.;Cohen, Eyal;Agrawal, Rishi;Mandl, Kenneth D.;Clifton, Holly;Neff, John
通讯作者：
Neff, John
DOI：
10.1016/j.jpeds.2020.06.020
发表时间：
2020-11
期刊：
The Journal of pediatrics
影响因子：
--
作者：
Freed AS;Clowes Candadai SV;Sikes MC;Thies J;Byers HM;Dines JN;Ndugga-Kabuye MK;Smith MB;Fogus K;Mefford HC;Lam C;Adam MP;Sun A;McGuire JK;DiGeronimo R;Dipple KM;Deutsch GH;Billimoria ZC;Bennett JT
通讯作者：
Bennett JT
影响因子：
8
作者：
Agrawal, Rishi;Hall, Matt;Berry, Jay G.
通讯作者：
Berry, Jay G.
影响因子：
14.9
作者：
Köhler S;Gargano M;Matentzoglu N;Carmody LC;Lewis-Smith D;Vasilevsky NA;Danis D;Balagura G;Baynam G;Brower AM;Callahan TJ;Chute CG;Est JL;Galer PD;Ganesan S;Griese M;Haimel M;Pazmandi J;Hanauer M;Harris NL;Hartnett MJ;Hastreiter M;Hauck F;He Y;Jeske T;Kearney H;Kindle G;Klein C;Knoflach K;Krause R;Lagorce D;McMurry JA;Miller JA;Munoz-Torres MC;Peters RL;Rapp CK;Rath AM;Rind SA;Rosenberg AZ;Segal MM;Seidel MG;Smedley D;Talmy T;Thomas Y;Wiafe SA;Xian J;Yüksel Z;Helbig I;Mungall CJ;Haendel MA;Robinson PN
通讯作者：
Robinson PN