Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting.

Frontiers in Immunology
Clair EngelbrechtBrigitte Glanzmann

Abstract

Primary immunodeficiency disorders (PIDs) are inborn errors of immunity (IEI) that cause immune system impairment. To date, more than 400 single-gene IEI have been well defined. The advent of next generation sequencing (NGS) technologies has improved clinical diagnosis and allowed for discovery of novel genes and variants associated with IEI. Molecular diagnosis provides clear clinical benefits for patients by altering management, enabling access to certain treatments and facilitates genetic counselling. Here we report on an 8-year experience using two different NGS technologies, namely research-based WES and targeted gene panels, in patients with suspected IEI in the South African healthcare system. A total of 52 patients' had WES only, 26 had a targeted gene panel only, and 2 had both panel and WES. Overall, a molecular diagnosis was achieved in 30% (24/80) of patients. Clinical management was significantly altered in 67% of patients following molecular results. All 24 families with a molecular diagnosis received more accurate genetic counselling and family cascade testing. Results highlight the clinical value of expanded genetic testing in IEI and its relevance to understanding the genetic and clinical spectrum of the IEI-re...Continue Reading

References

Jul 3, 2008·Annual Review of Genomics and Human Genetics·Michael C Campbell, Sarah A Tishkoff
Aug 1, 2012·Journal of Clinical Immunology·Ahmed Aziz BousfihaLaurent Abel
Apr 26, 2014·Current Protocols in Human Genetics·Wylie Burke
Jun 11, 2014·BMC Genomics·Chandra Sekhar Reddy ChilamakuriLeonardo A Meza-Zepeda
Oct 15, 2014·The Journal of Experimental Medicine·Jean-Laurent CasanovaLuigi D Notarangelo
Dec 17, 2014·BMC Medical Genomics·Dorin ManaseSeema Mital
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·Proceedings of the National Academy of Sciences of the United States of America·Aziz BelkadiLaurent Abel
Jun 26, 2015·Human Mutation·Eric SamorodnitskySameek Roychowdhury
Feb 27, 2016·The Journal of Allergy and Clinical Immunology·Hamoud Al-MousaAbbas Hawwari
Sep 1, 2016·The Journal of Allergy and Clinical Immunology·Asbjørg Stray-PedersenJames R Lupski
Nov 23, 2016·Frontiers in Immunology·Vera GalloClaudio Pignata
Aug 10, 2017·Frontiers in Immunology·Michael SelemanJanet Chou
Sep 14, 2017·Molecular Diagnosis & Therapy·Rabab E El HawaryAisha M Elmarsafy
Sep 26, 2014·South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde·B Eley, M Esser
Mar 6, 2018·Critical Reviews in Clinical Laboratory Sciences·Ana Esteve-SoléJacinta Bustamante
Apr 21, 2018·Journal of Clinical Immunology·Jennifer R HeimallRoshini S Abraham
Sep 7, 2018·Genes and Immunity·Brigitte GlanzmannCraig J Kinnear
Apr 30, 2019·Frontiers in Immunology·Cristina CifaldiGigliola Di Matteo
Sep 1, 2019·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·Javier ChinenLisa J Kobrynski
Feb 13, 2020·Journal of Clinical Immunology·Aziz BousfihaStuart G Tangye
Feb 23, 2020·Cardiovascular Drugs and Therapy·Francesco MazzarottoRoddy Walsh
Mar 7, 2020·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Amos J SimonRaz Somech
Dec 29, 2020·Frontiers in Immunology·Reetika Malik YadavManisha Rajan Madkaikar

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