Clinical, immunological and genomic characteristics of children with X-linked agammaglobulinemia from Kerala, South India

Hum Immunol. 2022 Jan 21:S0198-8859(22)00005-2. doi: 10.1016/j.humimm.2022.01.003. Online ahead of print.ABSTRACTX-linked agammaglobulinemia (XLA) is an X-linked recessive primary immunodeficiency disorder caused due to a pathogenic variant in the Bruton tyrosine (BTK) gene with an incidence of 1:379,000 live births and 1:190,000 male births. Patients affected with XLA present with recurrent infections of the gastrointestinal and respiratory tracts. Here we report the first case series of 17 XLA patients of 10 South Indian families with a wide spectrum of clinical and genetic features. In our cohort, patients presented mainly with recurrent pneumonia, gastrointestinal infection, otitis media, pyoderma, abscesses, empyema, arthritis, and osteomyelitis. Using next-generation and Sanger sequencing we have identified 10 unique pathogenic and likely pathogenic variants in 17 patients. This encompasses three nonsynonymous, two stop-gain, two frameshifts, two structural, and one splicing variant, out of which two of them are novel. Based on the type of variant, patients had variable clinical features and treatment responses. We have also evaluated Btk protein expression for six patients in comparison to the healthy individuals and determined mosaic Btk expression patterns in four mothers. We have also performed family screening in 6 families using Sanger sequencing and identified 19 carriers for the variant. The diagnosis for the patients led to the proper treatment i.e. 15 patients...

Source: Human Immunology - January 25, 2022 Category: Allergy & Immunology Authors: Geeta Madathil Govindaraj Abhinav Jain Athulya Edavazhippurath Rahul C Bhoyar Dhananjayan Dhanasooraj Anushree Mishra Vishu Gupta Mohandas Nair P M Shiny Ramya Uppuluri Anoop Kumar Atul Kashyap V T Ajith Kumar Gireesh Shankaran Vigneshwar Senthivel Mohame Source Type: research