Abstract
Clinical genetic sequencing is frequently utilized to diagnose individuals with neurodevelopmental disorders (NDDs). Here we perform a meta-analysis and systematic review of the success rate (diagnostic yield) of clinical sequencing through next-generation sequencing (NGS) across NDDs. We compare the genetic testing yield across NDD subtypes and sequencing technology. We performed a systematic review of the PubMed literature until May 2020. We included clinical sequencing studies that utilized NGS in individuals with epilepsy, autism spectrum disorder (ASD), or intellectual disability (ID). Data were extracted, reviewed, and categorized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators performed clinical evaluation and grouping following the International League Against Epilepsy (ILAE) guidelines. Pooled rates of the diagnostic yield and 95% confidence intervals were estimated with a random-effects model. We identified 103 studies (epilepsy, N = 72; ASD, N = 14; ID, N = 21) across 32,331 individuals. Targeted gene panel sequencing was used in 73, and exome sequencing in 36 cohorts. Given highly selected patient cohorts, the diagnostic yield was 17.1% for A...Continue Reading
References
Oct 6, 1997·BMJ : British Medical Journal·M EggerC Minder
Jul 6, 2000·Biometrics·S Duval, R Tweedie
Jul 22, 2009·PLoS Medicine·David MoherUNKNOWN PRISMA Group
Aug 10, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Vandana ShashiDavid G Goldstein
May 2, 2014·Human Molecular Genetics·Jacques L MichaudElsa Rossignol
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Apr 2, 2015·Australian and New Zealand Journal of Public Health·Priscilla Robinson, John Lowe
Sep 2, 2015·JAMA : the Journal of the American Medical Association·Kristiina TammimiesBridget A Fernandez
Oct 28, 2015·Nature Reviews. Genetics·Lisenka E L M VissersJoris A Veltman
Jul 22, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Aaron M WengerGill Bejerano
Nov 20, 2016·Human Mutation·Elena ParriniRenzo Guerrini
Mar 10, 2017·Epilepsia·Ingrid E SchefferSameer M Zuberi
Mar 24, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lisenka E L M VissersMichèl A A P Willemsen
Nov 22, 2017·American Journal of Medical Genetics. Part a·Bing XiaoYu Sun
Jan 13, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Caroline F WrightUNKNOWN DDD Study
Jun 6, 2018·JAMA Pediatrics·Christopher J YuskaitisAnnapurna Poduri
Jun 21, 2018·PloS One·Cha Gon LeeMunhyang Lee
Jun 27, 2018·Nature Genetics·Henrike O HeyneJohannes R Lemke
Aug 21, 2018·Clinical Genetics·Maryam Al-NabhaniAlmundher Al-Maawali
Oct 21, 2018·Epilepsia·Lisa-Marie NiestrojDennis Lal
Jan 6, 2019·Neurology·Iván Sánchez FernándezAnnapurna Poduri
Mar 25, 2019·Gene·Jinliang LiYuwu Jiang
Apr 6, 2019·Epilepsia·UNKNOWN Epilepsy Genetics Initiative
Jun 12, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Siddharth SrivastavaUNKNOWN NDD Exome Scoping Review WorkGroup
Aug 24, 2019·Epilepsia Open·Rebecca TrutySwaroop Aradhya
Aug 13, 2020·Epilepsia·David Lewis-Smith, Rhys H Thomas
Aug 13, 2020·Epilepsia·Guido RubboliKatrine M Johannesen
Citations
Jan 13, 2021·Current Opinion in Genetics & Development·Brenda M FinucaneJacob As Vorstman
May 1, 2021·Genes·Ana Arteche-LópezMaria Isabel Alvarez-Mora
Jul 17, 2021·European Journal of Human Genetics : EJHG·A Arteche-LópezM Moreno-García
Jul 25, 2021·Genome Research·Riley E PerszykStephen F Traynelis
Aug 8, 2021·Neurogenetics·Y TrakadisK Tabbane
Aug 3, 2021·Human Molecular Genetics·Gregory M Findlay
Sep 9, 2021·Neurology·Renzo GuerriniMatthew C Walker
Nov 7, 2021·Epilepsia·Nicola SpecchioPaolo Curatolo