Roifman Chaim M, Gu Yiping, Cohen Amos
Division of Immunology and Allergy and Program of Infection, Immunity, Injury and Repair, The Hospital for Sick Children and The University of Toronto, Ontario, Canada.
J Allergy Clin Immunol. 2006 Apr;117(4):897-903. doi: 10.1016/j.jaci.2006.01.003.
Omenn syndrome is a variant of severe combined immunodeficiency disease, which most prominently presents with erythroderma, eosinophilia, and susceptibility to various pathogens. Mutations in the nucleases of recombination activating genes 1 and 2 (RAG1/RAG2) or Artemis were found in some, but not all, patients with Omenn syndrome. We identified 2 patients who presented with clinical features consistent with Omenn syndrome but had no mutations in RAG or Artemis. Both patients also had cartilage-hair hypoplasia (CHH).
We sought to define the molecular basis and characterize the features of severe combined immunodeficiency and Omenn syndrome in these patients.
We have studied humoral and cellular immunity using standard assays. T-cell repertoire was investigated by quantitating Vbeta families. The RNase mitochondrial RNA processing (RMRP) RNA gene was sequenced by using standard techniques.
Sequence analysis of the RMRP RNA gene showed that each patient had an insertion-duplication on one allele and a point mutation on the other allele. These point mutations were novel, and they might be related to the unusual presentation of Omenn syndrome in addition to CHH in these patients. Indeed, analysis of the thymus showed residual mature T lymphocytes. This leaky thymus might be responsible for the skewed release of some T-cell clones into the circulation, which might trigger the phenotype of Omenn syndrome.
We have demonstrated that mutations in the RMRP RNA gene might be associated with Omenn syndrome.
This discovery will aid clinicians in the early recognition and treatment of CHH-associated Omenn syndrome.
奥门综合征是重症联合免疫缺陷病的一种变体，最显著的表现为红皮病、嗜酸性粒细胞增多以及对各种病原体易感。在部分但并非所有奥门综合征患者中发现了重组激活基因1和2（RAG1/RAG2）或Artemis核酸酶的突变。我们鉴定出2例具有与奥门综合征相符的临床特征但RAG或Artemis无突变的患者。这2例患者还患有软骨毛发发育不全（CHH）。
我们试图确定这些患者重症联合免疫缺陷和奥门综合征的分子基础并描述其特征。
我们使用标准检测方法研究了体液免疫和细胞免疫。通过定量Vβ家族来研究T细胞库。使用标准技术对核糖核酸酶线粒体RNA加工（RMRP）RNA基因进行测序。
RMRP RNA基因的序列分析显示，每位患者一个等位基因上有插入重复，另一个等位基因上有一个点突变。这些点突变是新发现的，除了CHH外，它们可能与这些患者奥门综合征的异常表现有关。事实上，胸腺分析显示有残留的成熟T淋巴细胞。这种渗漏的胸腺可能是导致一些T细胞克隆向循环中异常释放的原因，这可能引发奥门综合征的表型。
我们已证明RMRP RNA基因的突变可能与奥门综合征有关。
这一发现将有助于临床医生早期识别和治疗与CHH相关的奥门综合征。
