Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care.
Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care.
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DOI：
10.1111/cge.12654
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发表时间：
2016-03
影响因子：
3.5
通讯作者：
Boycott KM
中科院分区：
文献类型：
--
作者：
Sawyer SL;Hartley T;Dyment DA;Beaulieu CL;Schwartzentruber J;Smith A;Bedford HM;Bernard G;Bernier FP;Brais B;Bulman DE;Warman Chardon J;Chitayat D;Deladoëy J;Fernandez BA;Frosk P;Geraghty MT;Gerull B;Gibson W;Gow RM;Graham GE;Green JS;Heon E;Horvath G;Innes AM;Jabado N;Kim RH;Koenekoop RK;Khan A;Lehmann OJ;Mendoza-Londono R;Michaud JL;Nikkel SM;Penney LS;Polychronakos C;Richer J;Rouleau GA;Samuels ME;Siu VM;Suchowersky O;Tarnopolsky MA;Yoon G;Zahir FR;FORGE Canada Consortium;Care4Rare Canada Consortium;Majewski J;Boycott KM
准确的诊断是罕见遗传病儿童患者护理的一个组成部分。测序的最新进展，特别是全外显子组测序（WES），正在确定25-40%患者的疾病遗传基础。在诊断过程中，何时使用WES可能会影响诊断率。加拿大罕见疾病基因发现（FORGE）项目是一项全国性的努力，旨在使用WES识别儿童期发病疾病的突变。大多数参加FORGE项目的孩子都快结束诊断之旅了。FORGE的两个主要成果是新基因的发现和已知导致疾病的基因突变的鉴定。在后一种情况下，WES确定了362个研究家庭中105个（29%）已知疾病基因的突变，从而为WES在诊断奥德赛中的影响提供了信息。我们对该数据集的分析表明，这些已知的疾病基因在WES入组之前没有被识别，原因有两个：与临床诊断相关的遗传异质性和已知的临床公认疾病的非典型表现。越来越清楚的是，WES将改变罕见遗传病患者和家庭的模式。
An accurate diagnosis is an integral component of patient care for children with rare genetic disease. Recent advances in sequencing, in particular whole‐exome sequencing (WES), are identifying the genetic basis of disease for 25–40% of patients. The diagnostic rate is probably influenced by when in the diagnostic process WES is used. The Finding Of Rare Disease GEnes (FORGE) Canada project was a nation‐wide effort to identify mutations for childhood‐onset disorders using WES. Most children enrolled in the FORGE project were toward the end of the diagnostic odyssey. The two primary outcomes of FORGE were novel gene discovery and the identification of mutations in genes known to cause disease. In the latter instance, WES identified mutations in known disease genes for 105 of 362 families studied (29%), thereby informing the impact of WES in the setting of the diagnostic odyssey. Our analysis of this dataset showed that these known disease genes were not identified prior to WES enrollment for two key reasons: genetic heterogeneity associated with a clinical diagnosis and atypical presentation of known, clinically recognized diseases. What is becoming increasingly clear is that WES will be paradigm altering for patients and families with rare genetic diseases.
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DOI：
10.1038/gim.2013.73
发表时间：
2013-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4
作者：
Boycott K;Hartley T;Adam S;Bernier F;Chong K;Fernandez BA;Friedman JM;Geraghty MT;Hume S;Knoppers BM;Laberge AM;Majewski J;Mendoza-Londono R;Meyn MS;Michaud JL;Nelson TN;Richer J;Sadikovic B;Skidmore DL;Stockley T;Taylor S;van Karnebeek C;Zawati MH;Lauzon J;Armour CM;Canadian College of Medical Geneticists
通讯作者：
Canadian College of Medical Geneticists
影响因子：
3.7
作者：
Marcadier, Julien L.;Smith, Amanda M.;Geraghty, Michael T.
通讯作者：
Geraghty, Michael T.
影响因子：
8.8
作者：
Pyeritz, Reed E.
通讯作者：
Pyeritz, Reed E.
影响因子：
168.9
作者：
Rauch, Anita;Wieczorek, Dagmar;Strom, Tim M.
通讯作者：
Strom, Tim M.