A single-center pilot study in Malaysia on the clinical utility of whole-exome sequencing for inborn errors of immunity
Document Type
Article
Publication Date
11-1-2021
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.
Keywords
Bioinformatics analysis, Genetic diagnosis, Genetic variant, Inborn errors of immunity, Whole-exome sequencing
Divisions
InstituteofBiologicalSciences
Funders
Kementerian Kesihatan Malaysia [Grant No: NMRR--16--892--31023]
Publication Title
Clinical and Experimental Immunology
Volume
206
Issue
2
Publisher
Wiley
Publisher Location
111 RIVER ST, HOBOKEN 07030-5774, NJ USA