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Genet Med. 2015 Dec;17(12):995-1001. doi: 10.1038/gim.2015.21. Epub 2015 Mar 19.

A genome sequencing program for novel undiagnosed diseases.

Author information

1
Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.
2
Cypher Genomics, Inc., San Diego, California, USA.
3
Division of Pathology, Scripps Clinic, San Diego, California, USA.
4
Pediatrics, Scripps Health, San Diego, California, USA.
5
Department of Neurosciences, University of California San Diego, San Diego, California, USA.
6
Department of Pediatrics, University of California San Diego, San Diego, California, USA.
7
Division of Neurology, Scripps Clinic, San Diego, California, USA.
8
Division of Internal Medicine, Scripps Clinic, San Diego, California, USA.
9
Division of Gastroenterology/Hepatology, Scripps Clinic, San Diego, California, USA.
10
Division of Allergy and Immunology, Scripps Clinic, San Diego, California, USA.
11
Division of Rheumatology, Scripps Clinic, San Diego, California, USA.
12
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
13
Division of Cardiology, Scripps Clinic, San Diego, California, USA.
14
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.

Abstract

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.

PMID:
25790160
PMCID:
PMC4575596
DOI:
10.1038/gim.2015.21
[Indexed for MEDLINE]
Free PMC Article

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