Variable phenotype and discrete alterations of immune phenotypes in CTP synthase 1 deficiency: Report of 2 siblings

• Published in: Journal of allergy and clinical immunology 2016-12, Vol.138 (6), p.1722-1725.e6
• Main Authors: Trück, Johannes, MD, DPhil, Kelly, Dominic F., MRCP, PhD, Taylor, John M., PhD, Kienzler, Anne Kathrin, PhD, Lester, Tracy, FRCPath, PhD, Seller, Anneke, FRCPath, PhD, Pollard, Andrew J., FRCPCH, PhD, Patel, Smita Y., FRCP, FRCPath, PhD
• Format: Article
• Language: English
• Subjects: Age; Allergy and Immunology; Bacterial infections; Cell growth; Disease; Genotype & phenotype; Infections; Lymphocytes; Mutation; Patients; Siblings; Vaccines; Viral infections
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2016.04.059

To the Editor: Loss-of-function homozygous mutations in the CTP synthase 1 (CTPS1) gene in humans have only recently been discovered and reveal the role of this gene in lymphocyte proliferation.1 To date a single report including 8 individuals describes a severe clinical phenotype including early onset of severe chronic viral infections, recurrent encapsulated bacterial infections, and EBV-related B-cell non-Hodgkin lymphoma.1 We report 2 further sibling cases of CTSP1 deficiency identified through whole-exome sequencing (WES), further illustrating the phenotype of CTPS1 deficiency and demonstrating the value of WES for rapid diagnosis of primary immunodeficiency even for conditions whose phenotype is not well recognized. [...]memory B-cell frequencies may be normal in CTPS1-deficient patients before EBV exposure.\n Relative cell counts for CD4+ naive, term. diff., TCM, and TEM T cells depict the percentage of total CD4+ lymphocytes.