Lev Atar, Amariglio Ninette, Levy Yael, Spirer Zvi, Anikster Yair, Rechavi Gideon, Dekel Benjamin, Somech Raz
Cancer Research Center, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv, Israel.
Clin Immunol. 2009 Dec;133(3):375-81. doi: 10.1016/j.clim.2009.08.017. Epub 2009 Sep 30.
Schimke immuno-osseous dysplasia (SIOD) is caused by SMARCAL1 deficiency and characterized by defective T-cell immunity. The immunodeficiency and the role of thymic function in SIOD patients are not clearly understood. We performed thymic evaluations by assessing T-cell receptor (TCR) diversity, rearrangement, and excision circles in family members with different disease severity carrying the same bi-allelic mutation and in a heterozygous carrier. The expression of SMARCAL1 mRNA in a normal thymic sample was measured using real-time quantitative polymerase chain reaction. Thymus functions were significantly reduced in SIOD patients, and these findings were highly correlated with the clinical phenotype. Quantification of SMARCAL1 mRNA transcript was 3.86-fold higher than normal values for adult kidneys. Genotype alone apparently does not define phenotype, and analysis of TCR diversity, rearrangement, and thymus output can quantify the extent of T-cell immunodeficiency. High thymic expression of SMARCAL1 mRNA raises the possibility of its importance in thymus maintenance and function.
施姆克免疫性骨发育不良（SIOD）由SMARCAL1缺乏引起，其特征为T细胞免疫缺陷。SIOD患者的免疫缺陷以及胸腺功能的作用尚不清楚。我们通过评估携带相同双等位基因突变且疾病严重程度不同的家庭成员以及一名杂合携带者的T细胞受体（TCR）多样性、重排和切除环，对胸腺进行了评估。使用实时定量聚合酶链反应测量正常胸腺样本中SMARCAL1 mRNA的表达。SIOD患者的胸腺功能显著降低，这些发现与临床表型高度相关。SMARCAL1 mRNA转录本的定量比成人肾脏的正常值高3.86倍。仅基因型显然不能决定表型，对TCR多样性、重排和胸腺输出的分析可以量化T细胞免疫缺陷的程度。SMARCAL1 mRNA在胸腺中的高表达增加了其在胸腺维持和功能中具有重要性的可能性。
