Class II Transactivator Gene (CIITA) Variants Associated with Bare Lymphocyte Syndrome II in a Female Sudanese Patient

Omaima Abdel Majeed Mohamed Salih,1,2 Nahla Hashim Hassan Erwa,3 Abdelrahman Hamza Abdelmoneim,4 Hiba Awadelkareem Osman Fadl,5,6 Brigitte Glanzmann,7,8 Manasik Abdalla Babiker Osman,9 Monzir Ahmed Hassan Osman,10 Thuraya Mohamed Elshiekh Gasim,10 Alamin Mustafa4 1Departments of Pediatrics, Faculty of Medicine, Omdurman Islamic University, Omdurman, Sudan; 2Pediatric Clinical Immunologist, Tropical Disease Teaching Hospital, Omdurman, Sudan; 3Clinical Immunology Consultant, Faculty of Medicine & Soba University Hospital, University of Khartoum, Khartoum, Sudan; 4Faculty of Medicine, Al-Neelain University, Khartoum, Sudan; 5Department of Hematology, Faculty of Medical Laboratory Sciences, Al-Neelain University, Khartoum, Sudan; 6Senior Medical Laboratory Specialist, Saudi Commission for Health Specialties (SCFHS), Makkah, Kingdom of Saudi Arabia; 7DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7505, South Africa; 8South African Medical Research Council (SAMRC) Genomics Platform, Cape Town, 7505, South Africa; 9Faculty of Medicine, University of Bahri, Khartoum, Sudan; 10Faculty of Medicine and Health Sciences, Omdurman Islamic University, Khartoum, SudanCorrespondence: Alamin Mustafa, Faculty of Medicine, Al-Neelain University, JG37+2RM, 52nd St, Khartoum, Sudan, Email [email protected]: Inborn errors of immunity (IEI) are disorders that present a health issue, especially in developing countries where there is a high rate of consanguineous marriages and an increasing rate of diagnosis. One of these disorders is Bare Lymphocyte Syndrome II (BLS II) which is a rare and genetically complex disease that has high morbidity and mortality. The exact genotypic and phenotypic characteristics are still poorly characterized especially in developing countries.Case Presentation: Here, we report the first case of BLS II in a seven-month-old Sudanese female with recurrent chest infections, dermatitis, persistent diarrhea, and failure to thrive. The patient’s all four sisters and three paternal uncles died in early infancy. Laboratory investigations revealed low CD3+, CD4+, and CD8+ lymphocytes, along with normal CD19+ and CD16+ lymphocytes, and low serum IgM and IgA levels. Genetic analysis revealed two CIITA variants; c.2296C >G p. (Pro766Ala) and c.439+1G >A.Conclusion: Further bioinformatics, immunological and clinical workups supported a pathogenic effect of both mutations affecting the function of CIITA protein, and suggesting a compound heterozygote mutation. The patient was started on prophylactic antibiotics and regular intravenous immunoglobulin replacement therapy. The prognosis of this disease is poor in most of the cases, with only a few reported cases surviving until adulthood.Keywords: inborn errors of immunity, bare lymphocyte syndrome II, CIITA gene, compound heterozygote mutation, primary immunodeficiency