A genome sequencing program for novel undiagnosed diseases

被引：24

作者：

Bloss, Cinnamon S. ^{[1
]}

Zeeland, Ashley A. Scott-Van ^{[2
]}

Topol, Sarah E. ^{[1
]}

Darst, Burcu F. ^{[1
]}

Boeldt, Debra L. ^{[1
]}

Erikson, Galina A. ^{[1
]}

Bethel, Kelly J. ^{[3
]}

Bjork, Robert L. ^{[4
]}

Friedman, Jennifer R. ^{[5
,6
]}

Hwynn, Nelson ^{[7
]}

Patay, Bradley A. ^{[8
]}

Pockros, Paul J. ^{[9
]}

Scott, Erick R. ^{[1
]}

Simon, Ronald A. ^{[10
]}

Williams, Gary W. ^{[11
]}

Schork, Nicholas J. ^{[1
,12
]}

Topol, Eric J. ^{[1
,12
,13
]}

Torkamani, Ali ^{[1
,2
,12
,14
]}

机构：

[1] Scripps Genom Med, Scripps Hlth, San Diego, CA 92121 USA

[2] Cypher Genom Inc, San Diego, CA USA

[3] Scripps Clin, Div Pathol, San Diego, CA USA

[4] Scripps Hlth, Pediat, San Diego, CA USA

[5] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA

[6] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA

[7] Scripps Clin, Div Neurol, San Diego, CA USA

[8] Scripps Clin, Div Internal Med, San Diego, CA USA

[9] Scripps Clin, Div Gastroenterol Hepatol, San Diego, CA USA

[10] Scripps Clin, Div Allergy & Immunol, San Diego, CA USA

[11] Scripps Clin, Div Rheumatol, San Diego, CA USA

[12] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

[13] Scripps Clin, Div Cardiol, San Diego, CA USA

[14] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

来源：

GENETICS IN MEDICINE | 2015年 / 17卷 / 12期

基金：

美国国家卫生研究院;

关键词：

clinical sequencing; genome sequencing; genomics; rare disease; undiagnosed diseases; EXOME; MUTATIONS; DISCOVERY; GENETICS;

D O I：

10.1038/gim.2015.21

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Purpose: The Scripps Idiopathic Diseases of Man (IDIOM) study aims to discover novel gene-disease relationships and provide molecular genetic diagnosis and treatment guidance for individuals with novel diseases using genome sequencing integrated with clinical assessment and multidisciplinary case review. Here we describe the operational protocol and initial results of the IDIOM study. Methods: A total of 121 cases underwent first-tier review by the principal investigators to determine whether the primary inclusion criteria were satisfied, 59 (48.8%) underwent second-tier review by our clinician-scientist review panel, and 17 patients (14.0%) and their family members were enrolled. Results: 60% of cases resulted in a plausible molecular diagnosis, and 18% of cases resulted in a confirmed molecular diagnosis. Two of three confirmed cases led to the identification of novel gene-disease relationships. In the third confirmed case a previously described but unrecognized disease was revealed. In all three confirmed cases a new clinical management strategy was initiated based on the genetic findings. Conclusion: Genome sequencing provides tangible clinical benefit for individuals with idiopathic genetic disease, not only in the context of molecular genetic diagnosis of known rare conditions but also in cases where prior clinical information regarding a new genetic disorder is lacking.

引用

页码：995 / 1001

页数：7

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