A genome sequencing program for novel undiagnosed diseases

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Cinnamon S BlossAli Torkamani

Abstract

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. 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. 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. Genome sequencing provides tangible clinical benefit for individuals with idiopathic genetic disease, not only in the context of molecular genetic diagnosis of know...Continue Reading

References

May 1, 2009·Journal of Neuroscience Research·Kyoung-Shim Kim, Pyung-Lim Han
Dec 21, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Alan N MayerDavid A Margolis
Dec 22, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Elizabeth A WortheyDavid P Dimmock
Feb 15, 2011·Nature Genetics·Robert E HandsakerSteven A McCarroll
Nov 1, 2011·American Journal of Medical Genetics. Part a·Holly K TaborMichael J Bamshad
Jan 13, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·William A GahlDavid Adams
May 23, 2012·Nature Genetics·Magdalena HarakalovaEdwin Cuppen
Oct 5, 2012·The New England Journal of Medicine·Joep de LigtLisenka E L M Vissers
Jul 19, 2013·Science Translational Medicine·Howard J JacobElizabeth A Worthey
Sep 4, 2013·Nature Reviews. Genetics·Kym M BoycottAlex E MacKenzie
Oct 4, 2013·The New England Journal of Medicine·Yaping YangChristine M Eng
Apr 5, 2014·Annals of Neurology·Ying-Zhang ChenAli Torkamani
Apr 26, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Holly LaDucaElizabeth Chao
Jul 8, 2014·Oncogenesis·R BelaniA Torkamani
Aug 19, 2014·Annals of Neurology·Siddharth SrivastavaAli Fatemi
Aug 29, 2014·Annals of Neurology·Ali TorkamaniJennifer A Kearney
Oct 19, 2014·JAMA : the Journal of the American Medical Association·Yaping YangChristine M Eng
Nov 18, 2014·Nature Genetics·Mikko MuonaAnna-Elina Lehesjoki

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Citations

Aug 12, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kelly D Farwell HagmanSha Tang
Jul 1, 2016·Annual Review of Genomics and Human Genetics·Natasha T Strande, Jonathan S Berg
Apr 16, 2017·Circulation. Cardiovascular Genetics·Andrew R HarperEuan A Ashley
Dec 4, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Ranad ShaheenFowzan S Alkuraya
Jun 7, 2019·PloS One·Gabriella WasersteinMark Hyman Rapaport
Jan 1, 2017·Personalized Medicine·Debra L BoeldtCinnamon S Bloss
Nov 29, 2017·Frontiers in Cardiovascular Medicine·Manuel RuedaAli Torkamani
Aug 23, 2018·NPJ Genomic Medicine·Alireza HaghighiUNKNOWN Undiagnosed Diseases Network, Brigham and Women’s Hospital FaceBase Project, Brigham Genomic Medicine (BGM)
Aug 26, 2016·Expert Review of Molecular Diagnostics·Chiara Bacchelli, Hywel J Williams
Jan 8, 2016·Experimental Dermatology·Cristina Has
Jan 26, 2020·Journal of Medical Genetics·Brett DobleTony Roscioli

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Methods Mentioned

BETA
exome sequencing

Clinical Trials Mentioned

NCT01440218

Software Mentioned

Genome STRiP
IDIOM

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