Affiliations 

  • 1 Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, Ministry of Health, Selangor, Malaysia
  • 2 Pediatric Department, Penang General Hospital, Ministry of Health, Penang, Malaysia
  • 3 Pediatric Department, Kuala Lumpur Hospital, Ministry of Health, Kuala Lumpur, Malaysia
  • 4 Pediatric Department, Sultan Abdul Halim Hospital, Ministry of Health, Kedah, Malaysia
  • 5 Pediatric Department, Likas Hospital, Ministry of Health, Sabah, Malaysia
  • 6 Pediatric Department, Tuanku Ja'afar Hospital, Ministry of Health, Seremban, Malaysia
  • 7 Pediatric Department, Raja Permaisuri Bainun Hospital, Ministry of Health, Perak, Malaysia
  • 8 Pediatric Department, Sultan Ismail Johor Bahru Hospital, Ministry of Health, Johor, Malaysia
  • 9 Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
Clin Exp Immunol, 2021 Nov;206(2):119-128.
PMID: 34060650 DOI: 10.1111/cei.13626

Abstract

Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.