Gene Mutation of Interleukin-2 Receptor Common Gamma Chain in Four Male Infants with X-Linked Severe Combined Immunodeficiency

Abstract

Objective To analyse the relationship between clinical manifestations and the mutation of interleukin-2 receptor common gamma chain (IL-2RG) mutation of X-linked severe combined immunodeficiency (SCID) caused by IL-2RG. Methods From May 2010 to September 2012, four boys who were clinically suspected as X-linked SCID were enrolled in this study. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of West China Second University Hospital, Sichuan University.Informed consent was obtained from each participants' parents. IL-2RG mutation were detected and analyzed in four patients and their family members. Results Four boys were all suffered by severe pulmonary infection (severe pneumonia) and demonstrated to have absence of thymus or dysplastic thymus by chest X-ray film. Among them, three patients had tuberculosis infection after bacilli Calmette-Guerin (BCG) vaccination (75%), two patients had family history (50%), and all patients suffered lymphopenia (100%). All 4 male infants were demonstrated to be X-linked SCID due to the mutation of IL-2RG, including 2 patients with nonsense mutations (50%, c. 711.G>A, p. W237X and c. 578.G>A, p. W193X, respectively), one missense mutation (25%, c. 173C>A, p. P58Q), and 1 splice site mutation (25%, IVS5-2 G>T). The linear relatives of 3 patients and maternal relatives were detected the mutation of IL-2RG, and 3 patients were demonstrated to have family carriers (75%) and one patient was suffered by de novo mutation (25%). Conclusions The detection of IL-2RG gene mutation can confirm clinical diagnosis of X-linked SCID which is critical for patients to take hematopoietic stem cell transplantation as soon as possible to reconstruction of immunity before the fatal infection occurred. The early immune reconstruction can offer the best chance of long term survival. Key words: Severe combined immunodeficiency; Receptors, interleukin-2; Mutation