Open AccessNovel compound heterozygous stop‐gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency
Author(s) -
Phan Anh N. L.,
Pham Thuy T. T.,
Huynh Nghia,
Nguyen Tuan M.,
Cao Cuc T. T.,
Nguyen Duong T.,
Le Duc T.,
Bui ChiBao
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1216
Subject(s) - common variable immunodeficiency , hypogammaglobulinemia , compound heterozygosity , immunology , medicine , immune dysregulation , autoimmunity , exome sequencing , mutation , immune system , biology , genetics , antibody , gene
Background Lipopolysaccharide‐responsive and beige‐like anchor (LRBA) deficiency is a rare autosomal recessive common variable immunodeficiency (CVID), affecting 1:25,000–1:50,000 people worldwide. Biallelic mutations in the gene LRBA have been implicated in affected individuals. Methods We report a 16‐year‐old Vietnamese, male patient with recurrent CVID symptoms including chronic diarrhea, interstitial pneumonia, cutaneous granulomatous lesions, hepatosplenomegaly, and finger clubbing. Immunological analyses and whole exome sequencing (WES) were performed to investigate phenotypic and genotypic features. Results Immunological analyses revealed hypogammaglobulinemia and low ratios of CD4+/CD8+ T cells. Two novel compound heterozygous stop‐gain mutation in LRBA were identified: c.1933C > T (p.R645X) and c.949C > T (p.R317X). Sanger sequencing confirmed the segregation of these variants from the intact parents. The abolished LRBA protein expression was shown by immunoblot analysis. Subsequent treatment potentially saves the child from the same immune thrombocytopenia which led to his brother's untimely death; likely caused by the same LRBA mutations. Conclusion This first report of LRBA deficiency in Vietnam expands our knowledge of the diverse phenotypes and genotypes driving CVID. Finally, the utilization of WES shows great promise as an effective diagnostic for CVID in our setting.