Targeted next-generation sequencing for genetic diagnosis of 160 patients with primary immunodeficiency in south China

Abstract

Background: Primary immunodeficiency disorders (PID) is a group of heterogeneous diseases mainly characterized by severe and recurrent infections and an increased susceptibility to lymphoproliferative, atopic, and autoimmune conditions. The clinical diagnosis should preferably be complemented by a genetic diagnosis. To date, PID-related reports from China seldom attempt to make a genetic test for their patients.

Methods: Our study aimed to evaluate demographic data, clinical manifestations, and molecular diagnosis of PID patients from southern China. Moreover, by comparison with previous reports, we provide a picture of the current status of PID in mainland China. A total number of 160 pediatric PID patients (106 males and 54 females) were enrolled, and targeted next-generation sequencing was conducted using 269 PID-related genes and subsequently confirmed by Sanger sequencing and familial segregation analysis.

Result: The autoinflammatory disease group was the most common subcategory of PID (20%), followed by immune dysregulation (17.5%) and combined immunodeficiencies (16.2%). Antibody deficiency disorders were identified in only 11.9% of the cohort. The putative causative gene was identified in 70 patients (43.8%), and an X-linked pattern was found in 45.7% of the genetically diagnosed patients.

Conclusion: The current study provides the first collective study of PID phenotypes and genotypes in south China and provides a strong argument for the diagnostic application of targeted next-generation sequencing panels in patients with suspected PID.

Keywords: genetic diagnosis; primary immunodeficiency; targeted sequencing.