Brent L Fogel1, Saty Satya-Murti1, Bruce H Cohen1. 1. Program in Neurogenetics and Departments of Neurology and Human Genetics (BLF), David Geffen School of Medicine, University of California Los Angeles; Health Policy Consultant (SS-M), Santa Maria, CA; and NeuroDevelopmental Science Center and the Department of Pediatrics (BHC), Akron Children's Hospital, OH.
Abstract
PURPOSE OF REVIEW: The landscape of genetic diagnostic testing has changed dramatically with the introduction of next-generation clinical exome sequencing (CES), which provides an unbiased analysis of all protein-coding sequences in the roughly 21,000 genes in the human genome. Use of this testing, however, is currently limited in clinical neurologic practice by the lack of a framework for appropriate use and payer coverage. RECENT FINDINGS: CES can be cost-effective due to its high diagnostic yield in comparison to other genetic tests in current use and should be utilized as a routine diagnostic test in patients with heterogeneous neurologic phenotypes facing a broad genetic differential diagnosis. CES can eliminate the need for escalating sequences of conventional neurodiagnostic tests. SUMMARY: This review discusses the role of clinical exome sequencing in neurologic disease, including its benefits to patients, limitations, appropriate use, and billing. We also provide a reference template policy for payer use when considering testing requests.
PURPOSE OF REVIEW: The landscape of genetic diagnostic testing has changed dramatically with the introduction of next-generation clinical exome sequencing (CES), which provides an unbiased analysis of all protein-coding sequences in the roughly 21,000 genes in the human genome. Use of this testing, however, is currently limited in clinical neurologic practice by the lack of a framework for appropriate use and payer coverage. RECENT FINDINGS:CES can be cost-effective due to its high diagnostic yield in comparison to other genetic tests in current use and should be utilized as a routine diagnostic test in patients with heterogeneous neurologic phenotypes facing a broad genetic differential diagnosis. CES can eliminate the need for escalating sequences of conventional neurodiagnostic tests. SUMMARY: This review discusses the role of clinical exome sequencing in neurologic disease, including its benefits to patients, limitations, appropriate use, and billing. We also provide a reference template policy for payer use when considering testing requests.
Authors: Kornelia Neveling; Ilse Feenstra; Christian Gilissen; Lies H Hoefsloot; Erik-Jan Kamsteeg; Arjen R Mensenkamp; Richard J T Rodenburg; Helger G Yntema; Liesbeth Spruijt; Sascha Vermeer; Tuula Rinne; Koen L van Gassen; Danielle Bodmer; Dorien Lugtenberg; Rick de Reuver; Wendy Buijsman; Ronny C Derks; Nienke Wieskamp; Bert van den Heuvel; Marjolijn J L Ligtenberg; Hannie Kremer; David A Koolen; Bart P C van de Warrenburg; Frans P M Cremers; Carlo L M Marcelis; Jan A M Smeitink; Saskia B Wortmann; Wendy A G van Zelst-Stams; Joris A Veltman; Han G Brunner; Hans Scheffer; Marcel R Nelen Journal: Hum Mutat Date: 2013-10-18 Impact factor: 4.878
Authors: Brent L Fogel; Hane Lee; Joshua L Deignan; Samuel P Strom; Sibel Kantarci; Xizhe Wang; Fabiola Quintero-Rivera; Eric Vilain; Wayne W Grody; Susan Perlman; Daniel H Geschwind; Stanley F Nelson Journal: JAMA Neurol Date: 2014-10 Impact factor: 18.302
Authors: David T Miller; Margaret P Adam; Swaroop Aradhya; Leslie G Biesecker; Arthur R Brothman; Nigel P Carter; Deanna M Church; John A Crolla; Evan E Eichler; Charles J Epstein; W Andrew Faucett; Lars Feuk; Jan M Friedman; Ada Hamosh; Laird Jackson; Erin B Kaminsky; Klaas Kok; Ian D Krantz; Robert M Kuhn; Charles Lee; James M Ostell; Carla Rosenberg; Stephen W Scherer; Nancy B Spinner; Dimitri J Stavropoulos; James H Tepperberg; Erik C Thorland; Joris R Vermeesch; Darrel J Waggoner; Michael S Watson; Christa Lese Martin; David H Ledbetter Journal: Am J Hum Genet Date: 2010-05-14 Impact factor: 11.025
Authors: Sarah E Soden; Carol J Saunders; Laurel K Willig; Emily G Farrow; Laurie D Smith; Josh E Petrikin; Jean-Baptiste LePichon; Neil A Miller; Isabelle Thiffault; Darrell L Dinwiddie; Greyson Twist; Aaron Noll; Bryce A Heese; Lee Zellmer; Andrea M Atherton; Ahmed T Abdelmoity; Nicole Safina; Sarah S Nyp; Britton Zuccarelli; Ingrid A Larson; Ann Modrcin; Suzanne Herd; Mitchell Creed; Zhaohui Ye; Xuan Yuan; Robert A Brodsky; Stephen F Kingsmore Journal: Sci Transl Med Date: 2014-12-03 Impact factor: 17.956
Authors: Paldeep Singh Atwal; Marie-Louise Brennan; Rachel Cox; Michael Niaki; Julia Platt; Margaret Homeyer; Andrea Kwan; Sylvie Parkin; Susan Schelley; Leah Slattery; Yael Wilnai; Jonathan Adam Bernstein; Gregory M Enns; Louanne Hudgins Journal: Genet Med Date: 2014-02-13 Impact factor: 8.822
Authors: David Bick; Pamela C Fraser; Michael F Gutzeit; Jeremy M Harris; Tina M Hambuch; Daniel C Helbling; Howard J Jacob; Juliet N Kersten; Steven R Leuthner; Thomas May; Paula E North; Sasha Z Prisco; Bryce A Schuler; Mary Shimoyama; Kimberly A Strong; Scott K Van Why; Regan Veith; James Verbsky; Arthur M Weborg; Brandon M Wilk; Rodney E Willoughby; Elizabeth A Worthey; David P Dimmock Journal: J Pediatr Genet Date: 2016-11-28
Authors: H A Jinnah; Ron Alterman; Christine Klein; Joachim K Krauss; Elena Moro; Marie Vidailhet; Robert Raike Journal: J Neural Transm (Vienna) Date: 2017-02-03 Impact factor: 3.575
Authors: Kathie J Ngo; Jessica E Rexach; Hane Lee; Lauren E Petty; Susan Perlman; Juliana M Valera; Joshua L Deignan; Yuanming Mao; Mamdouh Aker; Jennifer E Posey; Shalini N Jhangiani; Zeynep H Coban-Akdemir; Eric Boerwinkle; Donna Muzny; Alexandra B Nelson; Sharon Hassin-Baer; Gemma Poke; Katherine Neas; Michael D Geschwind; Wayne W Grody; Richard Gibbs; Daniel H Geschwind; James R Lupski; Jennifer E Below; Stanley F Nelson; Brent L Fogel Journal: Hum Mutat Date: 2019-11-25 Impact factor: 4.700