Whole exome sequencing identifies compound heterozygous variants of CR2 gene in monozygotic twin patients with common variable immunodeficiency

Adiratna Mat Ripen; Hamidah Ghani; Chai Teng Chear; Mei Yee Chiow; Sharifah Nurul Husna Syed Yahya; Asiah Kassim; Saharuddin Bin Mohamad

doi:10.1177/2050312120922652

Whole exome sequencing identifies compound heterozygous variants of CR2 gene in monozygotic twin patients with common variable immunodeficiency

SAGE Open Med. 2020 May 22:8:2050312120922652. doi: 10.1177/2050312120922652. eCollection 2020.

Authors

Adiratna Mat Ripen¹, Hamidah Ghani², Chai Teng Chear¹, Mei Yee Chiow², Sharifah Nurul Husna Syed Yahya¹, Asiah Kassim³, Saharuddin Bin Mohamad^{2

4}

Affiliations

¹ Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, Ministry of Health, Kuala Lumpur, Malaysia.
² Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
³ Paediatric Institute, Kuala Lumpur Hospital, Ministry of Health, Kuala Lumpur, Malaysia.
⁴ Centre of Research in Systems Biology, Structural Bioinformatics and Human Digital Imaging (CRYSTAL), University of Malaya, Kuala Lumpur, Malaysia.

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.

Keywords: Respiratory medicine; allergy/immunology; paediatric; primary immunodeficiencies; whole exome sequencing.