Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Katherine L HelbigIngo Helbig

Abstract

To assess the yield of diagnostic exome sequencing (DES) and to characterize the molecular findings in characterized and novel disease genes in patients with epilepsy. In an unselected sample of 1,131 patients referred for DES, overall results were compared between patients with and without epilepsy. DES results were examined based on age of onset and epilepsy diagnosis. Positive/likely positive results were identified in 112/293 (38.2%) epilepsy patients compared with 210/732 (28.7%) patients without epilepsy (P = 0.004). The diagnostic yield in characterized disease genes among patients with epilepsy was 33.4% (105/314). KCNQ2, MECP2, FOXG1, IQSEC2, KMT2A, and STXBP1 were most commonly affected by de novo alterations. Patients with epileptic encephalopathies had the highest rate of positive findings (43.4%). A likely positive novel genetic etiology was proposed in 14/200 (7%) patients with epilepsy; this frequency was highest in patients with epileptic encephalopathies (17%). Three genes (COQ4, DNM1, and PURA) were initially reported as likely positive novel disease genes and were subsequently corroborated in independent peer-reviewed publications. DES with analysis and interpretation of both characterized and novel genetic e...Continue Reading

References

Jun 16, 2012·Science Translational Medicine·Tracy J Dixon-SalazarJoseph G Gleeson
Aug 7, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·UNKNOWN ACMG Board of Directors
Oct 5, 2012·The New England Journal of Medicine·Joep de LigtLisenka E L M Vissers
Feb 23, 2013·Current Opinion in Neurology·Ingo Helbig, Daniel H Lowenstein
Aug 10, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Vandana ShashiDavid G Goldstein
Aug 13, 2013·Nature·Andrew S AllenMelodie R Winawer
Aug 13, 2013·Neurology·Kazuyuki NakamuraHirotomo Saitsu
Oct 4, 2013·The New England Journal of Medicine·Yaping YangChristine M Eng
Nov 26, 2013·Annals of Neurology·Johannes R LemkeSarah Weckhuysen
Apr 16, 2014·Nature Reviews. Neurology·Rhys H Thomas, Samuel F Berkovic
Apr 26, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Holly LaDucaElizabeth Chao
May 17, 2014·Journal of Neurodevelopmental Disorders·Sébastien ChénierDimitri J Stavropoulos
Jun 6, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Alejandro IglesiasWendy K Chung
Jun 19, 2014·The New England Journal of Medicine·Leslie G Biesecker, Robert C Green
Aug 19, 2014·Annals of Neurology·Siddharth SrivastavaAli Fatemi
Sep 30, 2014·American Journal of Human Genetics·UNKNOWN EuroEPINOMICS-RES ConsortiumUNKNOWN Epi4K Consortium
Oct 19, 2014·JAMA : the Journal of the American Medical Association·Yaping YangChristine M Eng
Oct 31, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kelly D FarwellSha Tang
Nov 25, 2014·Nature Communications·B J O'RoakE E Eichler
Dec 24, 2014·Nature·UNKNOWN Deciphering Developmental Disorders Study
Feb 7, 2015·American Journal of Human Genetics·Gloria Brea-CalvoDaniele Ghezzi
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Mar 31, 2015·Epilepsia·Saadet Mercimek-MahmutogluO Carter Snead
Apr 22, 2015·Lancet Neurology·Daniel H Geschwind, Matthew W State

❮ Previous
Next ❯

Citations

Jun 24, 2016·Journal of Medical Genetics·Jonatan HalvardsonLars Feuk
Jan 7, 2017·Journal of Child Neurology·Lacey A SmithAnnapurna Poduri
Mar 16, 2017·European Journal of Human Genetics : EJHG·Lisa J EwansCheryl Shoubridge
May 27, 2017·Expert Review of Molecular Diagnostics·Yvonne G WeberHolger Lerche
Jun 20, 2017·Nature Neuroscience·Madeleine R GeishekerEvan E Eichler
Dec 30, 2017·Clinical Genetics·B TumienėB Peterlin
Jan 20, 2018·Journal of Neurosurgery. Pediatrics·Daniel DuranKristopher T Kahle
May 10, 2018·Epilepsia·Ingo HelbigUNKNOWN International League Against Epilepsy Genetics Commission
Nov 3, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sophie NambotUNKNOWN Orphanomix Physicians' Group
Dec 1, 2017·PloS One·Laura Ortega-MorenoUNKNOWN Grupo Español de Genética de las Epilepsias de la Infancia (GEGEI)
Aug 28, 2018·PloS One·Kamel JabbariPeter Nürnberg
May 16, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Hadley Stevens SmithHeidi V Russell
Jan 16, 2019·Der Nervenarzt·Michael ZechJuliane Winkelmann
Jan 22, 2019·Expert Review of Molecular Diagnostics·Rikke S MøllerKatrine M Johannesen
Feb 27, 2019·Current Neurology and Neuroscience Reports·Sean T HwangSimona V Proteasa
May 6, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Henrike O HeyneJohannes R Lemke
Dec 6, 2017·European Journal of Human Genetics : EJHG·Nicolas LebrunThierry Bienvenu
Jul 30, 2019·Annals of Clinical and Translational Neurology·Joohyun ParkTobias B Haack
Aug 14, 2019·Annals of Clinical and Translational Neurology·Jaya PunethaJames R Lupski
Sep 4, 2019·Epilepsy Currents·Heather C Mefford
Oct 28, 2019·Human Genome Variation·Yuji NakamuraShinji Saitoh
Jan 6, 2019·Neurology·Iván Sánchez FernándezAnnapurna Poduri
Jul 2, 2017·Neurology·Sarah von SpiczakUNKNOWN EuroEPINOMICS-RES NLES Working Group
Oct 28, 2019·Autism Research : Official Journal of the International Society for Autism Research·Lu XiaFengyu Zhang
Mar 24, 2020·Brain : a Journal of Neurology·David Lewis-SmithRhys H Thomas
Apr 8, 2020·Genetic Testing and Molecular Biomarkers·David StaněkPetra Laššuthová
Dec 2, 2017·American Journal of Medical Genetics. Part a·Darius Ebrahimi-FakhariUNKNOWN CureSPG47
Apr 9, 2020·American Journal of Medical Genetics. Part a·Emily M BryantJoel Charrow
Jul 4, 2020·American Journal of Medical Genetics. Part a·Omotayo OpeAndrew K Sobering
Jul 16, 2019·Brain : a Journal of Neurology·Joseph D SymondsMargaret Wilson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.