Whole exome sequencing identifies compound heterozygous variants ofCR2gene in monozygotic twin patients with common variable immunodeficiency

Abstract

Objectives: A pair of female Malay monozygotic twins who presented with recurrent upper respiratory tract infections, hepatosplenomegaly, bronchiectasis and bicytopenia were recruited in this study. Both patients were suspected with primary immunodeficiency diseases. However, the definite diagnosis was not clear due to complex disease phenotypes. The objective of this study was to identify the causative gene mutation in these patients. Methods: Lymphocyte subset enumeration test and whole exome sequencing were performed. Results: We identified a compound heterozygous CR2 mutation (c.1916G>A and c.2012G>A) in both patients. These variants were then confirmed using Sanger sequencing. Conclusion: Whole exome sequencing analysis of the monozygotic twins revealed compound heterozygous missense mutations in CR2.

Functional genomics in inborn errors of immunity

“…Hyper IgE syndrome can also be caused, however, in an autosomal recessive fashion due to homozygous variants in ZNF341 , 131,132 and there are both autosomal dominant and autosomal recessive forms driven by distinct mutations gp130 (encoded by IL6ST ) 133,134 . Autosomal recessive IEI can also be driven by compound heterozygosity in which two distinct deleterious alleles are inherited 135–137 . Still more complicated would be the interaction of variants across a small number of genes.…”

“…133,134 Autosomal recessive IEI can also be driven by compound heterozygosity in which two distinct deleterious alleles are inherited. [135][136][137] Still more complicated would be the interaction of variants across a small number of genes. As the number of involved genes increases from one, comprehensive identification of the causal variants is increasingly difficult, though to develop computational tools to facilitate analysis of these so-called oligogenic disorders is underway.…”