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

Abstract

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. 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. 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. 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.