Lack of nonfunctional B-cell receptor rearrangements in a patient with normal B cell numbers despite partial RAG1 deficiency and atypical SCID/Omenn syndrome
Lack of nonfunctional B-cell receptor rearrangements in a patient with normal B cell numbers despite partial RAG1 deficiency and atypical SCID/Omenn syndrome
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DOI：
10.1007/s10875-008-9210-7
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发表时间：
2008-09-01
影响因子：
9.1
通讯作者：
Barington, Torben
中科院分区：
文献类型：
--
作者：
Ohm-Laursen, Line;Nielsen, Christian;Barington, Torben
介绍一个2.5个月大的男孩提出了反复喘息，长期腹泻，红皮病，和失败thrived.Methods和结果实验室分析显示淋巴细胞减少，T细胞数量严重减少，但正常数量的B和NK细胞。血清IgE升高，患者出现嗜酸性粒细胞增多。这些表现与非典型严重联合免疫缺陷（SCID）/Omenn综合征一致，诊断通过RAG 1催化核心中R841 W突变的纯合性证实。将患者的免疫球蛋白重链重排与年龄匹配的对照组、脐带血和成人的免疫球蛋白重链重排进行比较，发现几乎完全没有非生产性重排（2.7%对比对照组的14.7%、27.6%和19.8%，（三）未按规定改正的;结论我们推测R841 W突变导致RAG 1基因功能异常，并在V（D）上产生不同的结果。B和T细胞中的J重组，因为患者具有正常的B细胞数量，但患有严重的α-β T细胞免疫缺陷。
Introduction A 2.5-month old boy presented with recurrent wheezing, protracted diarrhea, erythrodermia, and failure to thrive.Methods and Results Laboratory analysis showed lymphocytopenia with severely reduced T-cell numbers but normal numbers of B and NK cells. Serum IgE was increased and the patient had eosinophilia. These presentations are consistent with atypical severe combined immunodeficiency (SCID)/Omenn Syndrome and the diagnosis was confirmed by demonstration of homozygosity for the R841W mutation in the catalytic core of RAG1. Comparison of the patient's immunoglobulin heavy chain rearrangements to those of age-matched controls, cord blood, and adults revealed an almost total lack of nonproductive rearrangements (2.7% versus 14.7%, 27.6%, and 19.8% in the controls, respectively) indicating failure to correct out-of-frame rearrangements by a second rearrangement on the homologous chromosome 14.Conclusion We hypothesize that the R841W mutation causes a malfunction of RAG1 that has differential outcome on V(D)J recombination in B and T cells, as the patient had normal B cell numbers but suffered severe alpha-beta T-cell immunodeficiency.