Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome
Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome
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DOI：
10.1182/blood-2008-04-149708
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发表时间：
2008-09-01
期刊：
影响因子：
20.3
通讯作者：
Yachie, Akihiro
中科院分区：
文献类型：
--
作者：
Wada, Taizo;Yasui, Masahiro;Yachie, Akihiro
X连锁严重联合免疫缺陷（XSCID）是由常见γ链（γ c）突变引起的，通常以缺乏T和自然杀伤（INK）细胞为特征。在这里，我们报告了一个非典型的情况下，XSCID提出自体T和INK细胞和Omenn综合征样表现。该患者携带剪接位点突变（IVS1+5G > A），导致大部分mRNA被错误剪接，但产生少量正常剪接的转录本，导致残留的γ c表达和T细胞和INK细胞的发育。皮肤活检标本显示大量的回复突变T细胞浸润。这些T细胞被发现具有第二位点突变，并导致正确剪接的完全恢复。这些研究结果表明，XSCID的临床谱是相当广泛的，包括模仿Omenn综合征的非典型病例，并强调了作为可变表型表达的可能原因的回复突变嵌合体的重要性。
X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain (gamma c) and usually characterized by the absence of T and natural killer (INK) cells. Here, we report an atypical case of XSCID presenting with autologous T and INK cells and Omenn syndrome-like manifestations. The patient carried a splice-site mutation (IVS1+5G > A) that caused most of the mRNA to be incorrectly spliced but produced normally spliced transcript in lesser amount, leading to residual gamma c expression and development of T and INK cells. The skin biopsy specimen showed massive infiltration of revertant T cells. Those T cells were found to have a second-site mutation and result in complete restoration of correct splicing. These findings suggest that the clinical spectrum of XSCID is quite broad and includes atypical cases mimicking Omenn syndrome, and highlight the importance of revertant mosaicism as a possible cause for variable phenotypic expression.