Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)

Sanyal, Mrinmoy (55506354600)Mrinmoy (55506354600)SanyalMorimoto, Marie (54400133600)Marie (54400133600)MorimotoBaradaran-Heravi, Alireza (24576318700)Alireza (24576318700)Baradaran-HeraviChoi, Kunho (7403949485)Kunho (7403949485)ChoiKambham, Neeraja (6603340119)Neeraja (6603340119)KambhamJensen, Kent (56316571300)Kent (56316571300)JensenDutt, Suparna (8323822500)Suparna (8323822500)DuttDionis-Petersen, Kira Y. (56925380200)Kira Y. (56925380200)Dionis-PetersenLiu, Lan Xiang (56923886400)Lan Xiang (56923886400)LiuFelix, Katie (56924910800)Katie (56924910800)FelixMayfield, Christy (36480369200)Christy (36480369200)MayfieldDekel, Benjamin (7004279520)Benjamin (7004279520)DekelBokenkamp, Arend (7003677203)Arend (7003677203)BokenkampFryssira, Helen (6602617953)Helen (6602617953)FryssiraGuillen-Navarro, Encarna (14028300200)Encarna (14028300200)Guillen-NavarroLama, Giuliana (55298071600)Giuliana (55298071600)LamaBrugnara, Milena (22984429500)Milena (22984429500)BrugnaraLücke, Thomas (7004154235)Thomas (7004154235)LückeOlney, Ann Haskins (57216387044)Ann Haskins (57216387044)OlneyHunley, Tracy E. (6602466725)Tracy E. (6602466725)HunleyPolat, Ayse Ipek (56704609600)Ayse Ipek (56704609600)PolatYis, Uluc (8688659000)Uluc (8688659000)YisBogdanovic, Radovan (7004665744)Radovan (7004665744)BogdanovicMitrovic, Katarina (23498072800)Katarina (23498072800)MitrovicBerry, Susan (7201836853)Susan (7201836853)BerryNajera, Lydia (6603294178)Lydia (6603294178)NajeraNajafian, Behzad (7801350425)Behzad (7801350425)NajafianGentile, Mattia (35555538300)Mattia (35555538300)GentileNur Semerci, C. (59158278300)C. (59158278300)Nur SemerciTsimaratos, Michel (55987886400)Michel (55987886400)TsimaratosLewis, David B. (7404750928)David B. (7404750928)LewisBoerkoel, Cornelius F. (6701809729)Cornelius F. (6701809729)Boerkoel2025-07-022025-07-022015https://doi.org/10.1016/j.clim.2015.10.005https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945308414&doi=10.1016%2fj.clim.2015.10.005&partnerID=40&md5=83d3bed24abbae8346e00e758518dcfdhttps://remedy.med.bg.ac.rs/handle/123456789/13526Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7Rα) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients. © 2015 Elsevier Inc.CD127CpGIL7RαPromoter DNA methylationSIODT-cell immunodeficiencyLack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)