Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.
Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.
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DOI：
10.1038/gim.2017.119
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Marshall CR
中科院分区：
文献类型：
--
作者：
Lionel AC;Costain G;Monfared N;Walker S;Reuter MS;Hosseini SM;Thiruvahindrapuram B;Merico D;Jobling R;Nalpathamkalam T;Pellecchia G;Sung WWL;Wang Z;Bikangaga P;Boelman C;Carter MT;Cordeiro D;Cytrynbaum C;Dell SD;Dhir P;Dowling JJ;Heon E;Hewson S;Hiraki L;Inbar-Feigenberg M;Klatt R;Kronick J;Laxer RM;Licht C;MacDonald H;Mercimek-Andrews S;Mendoza-Londono R;Piscione T;Schneider R;Schulze A;Silverman E;Siriwardena K;Snead OC;Sondheimer N;Sutherland J;Vincent A;Wasserman JD;Weksberg R;Shuman C;Carew C;Szego MJ;Hayeems RZ;Basran R;Stavropoulos DJ;Ray PN;Bowdin S;Meyn MS;Cohn RD;Scherer SW;Marshall CR
基因检测是儿科医学不可或缺的诊断组成部分。护理标准通常是一种耗时的逐步方法，涉及染色体微阵列分析和靶向基因测序面板，这可能是昂贵的和不确定的。全基因组测序（WGS）提供了一个全面的测试平台，有可能简化遗传评估，但有有限的比较数据来指导其临床应用。我们前瞻性地从儿科非遗传亚专科诊所招募了103例患者，每例患者的临床表型均提示潜在的遗传疾病，并将WGS的诊断率和覆盖率与常规基因检测进行了比较。WGS在41%的个体中识别出诊断变异，比传统检测结果显著增加（24% P = 0.01）。队列中临床测序的基因（n = 1，226）被WGS充分覆盖，外显子覆盖率中位数为40 × ±8 ×（平均值±SD）。所有通过常规方法进行的分子诊断都被WGS捕获。使用WGS进行的18项新诊断包括全外显子组测序无法检测到的结构和非外显子序列变异，并证实了与PIGG，RNU4ATAC，TRIO和UNC13A基因的近期疾病相关性。在临床异质性队列中，WGS作为主要临床试验提供了比常规基因检测更高的诊断率。
Genetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use. We prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing. WGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24% P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A. WGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.
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影响因子：
4
作者：
Heinen CA;Jongejan A;Watson PJ;Redeker B;Boelen A;Boudzovitch-Surovtseva O;Forzano F;Hordijk R;Kelley R;Olney AH;Pierpont ME;Schaefer GB;Stewart F;van Trotsenburg AS;Fliers E;Schwabe JW;Hennekam RC
通讯作者：
Hennekam RC
DOI：
10.1056/nejmoa1516767
发表时间：
2017-01-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Posey JE;Harel T;Liu P;Rosenfeld JA;James RA;Coban Akdemir ZH;Walkiewicz M;Bi W;Xiao R;Ding Y;Xia F;Beaudet AL;Muzny DM;Gibbs RA;Boerwinkle E;Eng CM;Sutton VR;Shaw CA;Plon SE;Yang Y;Lupski JR
通讯作者：
Lupski JR
DOI：
10.1212/nxg.0000000000000105
发表时间：
2016-10
期刊：
Neurology. Genetics
影响因子：
--
作者：
Engel AG;Selcen D;Shen XM;Milone M;Harper CM
通讯作者：
Harper CM
影响因子：
8.8
作者：
Kalia, Sarah S.;Adelman, Kathy;Miller, David T.
通讯作者：
Miller, David T.
影响因子：
16.6
作者：
Merico, Daniele;Roifman, Maian;Scherer, Stephen W.
通讯作者：
Scherer, Stephen W.