Division of Immunology, Children's Hospital, Chongqing Medical University, Chongqing, China.
Pediatr Allergy Immunol. 2011 Aug;22(5):482-7. doi: 10.1111/j.1399-3038.2010.01126.x. Epub 2011 Mar 29.
Omenn syndrome (OS) is a rare autosomal recessive genetic disorder and presents symptoms of severe combined immunodeficiency characterized by erythrodermia, eosinophilia, hepatosplenomegaly, lymphadenopathy, and elevated serum IgE levels. OS has been found to be caused by mutations in RAG1 or RAG2 gene that result in partial V(D)J recombination activity. No study on OS has been reported in Chinese children so far. In this study, the genotype and phenotypes of three infants with OS from three unrelated Chinese families were investigated. All the three children had most of the characteristics of OS except normal serum IgE level. Compound heterozygosity mutations in RAG1 gene (1983 G>A; 2444 C>T and 2219 C>T; 3127 C>G) were identified in two cases, and a homozygous deletion mutation with a premature stop codon was found at residue 2302 of RAG1 gene (2302delT, I729X) in the remaining case, including three novel mutations (2302delT, I729X; 2219 C>T, R699W; and 3127 C>G, Y1001X). Spectratyping analysis of T-cell receptor β-chain variable region (TCRVβ) gene rearrangement was performed in case 1 and case 2. All the 25 TCRVβ subfamilies presented monoclonal or oligoclonal peaks in case 1 and 11 TCRVβ subfamilies were very weak or even absent in case 2. This was the first report about OS in Chinese children. Molecular genetic testing represents an important tool for early confirmed diagnosis and may allow accurate carrier detection and prenatal diagnosis.
先天性全免疫缺陷病伴免疫球蛋白 E 水平升高综合征（OS）是一种罕见的常染色体隐性遗传疾病，表现为严重联合免疫缺陷特征，包括红皮病、嗜酸性粒细胞增多、肝脾肿大、淋巴结病和血清 IgE 水平升高。OS 已被发现是由 RAG1 或 RAG2 基因突变引起的，导致部分 V(D)J 重组活性缺失。目前为止，尚未有关于中国儿童 OS 的报道。本研究调查了来自 3 个无关中国家庭的 3 例 OS 婴儿的基因型和表型。除了正常的血清 IgE 水平外，所有 3 例患儿均具有 OS 的大部分特征。2 例患儿 RAG1 基因存在复合杂合突变（1983 G>A；2444 C>T 和 2219 C>T；3127 C>G），另 1 例患儿 RAG1 基因存在 2302 位核苷酸缺失并导致移码突变（2302delT，I729X），包括 3 个新突变（2302delT，I729X；2219 C>T，R699W；和 3127 C>G，Y1001X）。对 1 例和 2 例患儿的 T 细胞受体 β 链可变区（TCRVβ）基因重排进行了谱型分析。在病例 1 中，所有 25 个 TCRVβ 亚家族均呈现单克隆或寡克隆峰，而在病例 2 中，11 个 TCRVβ 亚家族非常微弱甚至缺失。这是中国儿童 OS 的首例报道。分子遗传学检测是早期确诊的重要工具，可实现准确的携带者检测和产前诊断。
