Work

A Novel RAC2 Mutation Causing Combined Immunodeficiency

Year: 2022

Type: article

Abstract: Purpose Ras-related C3 botulinum toxin substrate 2 (RAC2) acts as a molecular switch and has crucial roles in cell signaling and actin dynamics. A broad spectrum of genetic RAC2 mutations can cause various types of primary immunodeficiency, with complete penetrance. Here, we report a novel heterozygous missense mutation in RAC2 and the associated phenotypes in a Chinese family. Methods Immunological phenotype was detected by flow cytometry. T-cell receptor excision circles (TRECs) and K-deleting recombination excision circles (KRECs) were assessed by real-time quantitative PCR. Gene mutations were detected by whole-exome sequencing (WES) and confirmed by Sanger sequencing. Results The proband was an 11-year-old girl who presented with recurrent respiratory infections, bronchiectasis, persistent Epstein-Barr virus viremia, infectious mononucleosis, encephalitis, and cutaneous human papillomavirus infections. Laboratory analyses revealed increased serum IgG and decreased IgM levels, reduced naïve CD4+ and CD8+ T cells, an inverted CD4+/CD8+ ratio, and low TREC and KREC numbers. WES identified a c.44G > A mutation in RAC2 resulting in a p.G15D substitution. The proband’s father suffered with recurrent respiratory infections and bronchiectasis, while her sister was apparently healthy, other than cutaneous human papillomavirus infections, despite both sharing the same mutation as the proband. Conclusions Our findings broaden the clinical and genetic spectra of RAC2 mutations and underline the importance of RAC2 gain-of-function mutations with complete or incomplete penetrance.

Source: Journal of Clinical Immunology

DOI: 10.1007/s10875-022-01373-8