Novel exonic mutation inducing aberrant splicing in the IL10RA gene and resulting in infantile-onset inflammatory bowel disease: a case report.
Novel exonic mutation inducing aberrant splicing in the IL10RA gene and resulting in infantile-onset inflammatory bowel disease: a case report.
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DOI：
10.1186/s12876-016-0424-5
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发表时间：
2016-01-28
影响因子：
2.4
通讯作者：
Yamamoto K
中科院分区：
文献类型：
--
作者：
Yanagi T;Mizuochi T;Takaki Y;Eda K;Mitsuyama K;Ishimura M;Takada H;Shouval DS;Griffith AE;Snapper SB;Yamashita Y;Yamamoto K
尽管白介素10及其受体分子的有害突变会导致严重的婴儿期炎症性肠病，但目前还没有日本患者的突变影响这一信号通路的报道。在这里，我们报告了IL10RA基因的一个新的外显子突变，该突变导致了一名日本婴儿发病的炎症性肠病与免疫性血小板减少性紫癜和类似幼年粒单核细胞白血病的短暂临床综合征相关的独特剪接异常。一名日本男孩，父母是非血缘关系健康的第一个孩子，在婴儿早期就出现了血性腹泻、肛周瘘和毛囊炎，并被诊断为炎症性肠病。他还出现了免疫性血小板减少性紫癜和青少年粒单核细胞白血病的一过性特征。患者对各种治疗无效，包括基本饮食、沙拉唑磺胺吡啶、甲硝唑、皮质类固醇、英夫利昔单抗和阿达利单抗。我们在IL10RA基因外显子4中发现了一个新的突变(c.537G >； A，p.T179T)，导致了独特的剪接异常，并导致了通过白细胞介素10受体缺乏信号。在21个月大的时候，患者接受了异基因造血干细胞移植，并获得了临床缓解。我们描述了一种新的IL10RA基因外显子突变导致婴儿发作性炎症性肠病。这种突变也可能与他的早发性血液病有关。内科医生应该熟悉IL-10信号缺陷的临床表型，以便能够在早期及时诊断并推荐异基因造血干细胞移植。本文的在线版本(doi：10.1186/s12876-0160424-5)包含补充材料，授权用户可以使用。
Although deleterious mutations in interleukin-10 and its receptor molecules cause severe infantile-onset inflammatory bowel disease, there are no reports of mutations affecting this signaling pathway in Japanese patients. Here we report a novel exonic mutation in the IL10RA gene that caused unique splicing aberrations in a Japanese patient with infantile-onset of inflammatory bowel disease in association with immune thrombocytopenic purpura and a transient clinical syndrome mimicking juvenile myelomonocytic leukemia. A Japanese boy, who was the first child of non-consanguineous healthy parents, developed bloody diarrhea, perianal fistula, and folliculitis in early infancy and was diagnosed with inflammatory bowel disease. He also developed immune thrombocytopenic purpura and transient features mimicking juvenile myelomonocytic leukemia. The patient failed to respond to various treatments, including elemental diet, salazosulfapyridine, metronidazole, corticosteroid, infliximab, and adalimumab. We identified a novel mutation (c.537G > A, p.T179T) in exon 4 of the IL10RA gene causing unique splicing aberrations and resulting in lack of signaling through the interleukin-10 receptor. At 21 months of age, the patient underwent allogeneic hematopoietic stem cell transplantation and achieved clinical remission. We describe a novel exonic mutation in the IL10RA gene resulting in infantile-onset inflammatory bowel disease. This mutation might also be involved in his early-onset hematologic disorders. Physicians should be familiar with the clinical phenotype of IL-10 signaling defects in order to enable prompt diagnosis at an early age and referral for allogeneic hematopoietic stem cell transplantation. The online version of this article (doi:10.1186/s12876-016-0424-5) contains supplementary material, which is available to authorized users.