Primary immunodeficiency with chronic enteropathy and developmental delay in a boy arising from a novel homozygous RIPK1 variant
Primary immunodeficiency with chronic enteropathy and developmental delay in a boy arising from a novel homozygous RIPK1 variant
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男孩因新型纯合 RIPK1 变异引起的原发性免疫缺陷伴慢性肠病和发育迟缓
DOI：
10.1038/s10038-019-0631-3
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发表时间：
2019
影响因子：
3.5
通讯作者：
Mizuguchi Takesh
中科院分区：
文献类型：
--
作者：
Uchiyama Yuri;Kim Chong A;Pastorino Antonio Carlos;Ceroni Jos?;Lima Patricia Picciarelli;de Barros Dorna Mayra;Honjo Rachel Sayuri;Bertola D?bora;Hamanaka Kohei;Fujita Atsushi;Mitsuhashi Satomi;Miyatake Satoko;Takata Atsushi;Miyake Noriko;Mizuguchi Takesh
确定原发性单基因免疫缺陷的遗传原因将加强目前对其免疫病理学的理解。与肿瘤坏死因子α（TNFα）信号传导相关的致病性基因变异，包括OTULIN、TNFAIP 3、RBCK 1和RNF 31，可引起伴有或不伴有免疫缺陷的人类先天性自身炎症性疾病。RIPK 1编码一种与受体相互作用的丝氨酸/苏氨酸激酶1，存在于介导信号传导的蛋白复合物中，包括TNF受体1。RIPK 1的双等位基因功能丧失变异体最近在患有原发性免疫缺陷的肠疾病和关节炎的个体中被报道。在这里，我们报告了一个新的同源RIPK 1变异的男孩与免疫缺陷和慢性肠病。我们的病人表现出严重的运动迟缓和轻度智力残疾，这是以前未知的。本研究结果有望加深对RIPK 1异常的临床特征的认识。
Identification of genetic causes of primary monogenic immunodeficiencies would strengthen the current understanding of their immunopathology. Pathogenic variants in genes in association with tumor necrosis factor α (TNFα) signaling, includingOTULIN, TNFAIP3, RBCK1, andRNF31cause human congenital autoinflammatory diseases with/without immunodeficiency.RIPK1, encoding a receptor interacting serine/threonine kinase 1, is present in protein complexes mediating signal transduction including TNF receptor 1. Biallelic loss-of-function variants inRIPK1were recently reported in individuals with primary immunodeficiency with intestinal bowel disease and arthritis. Here, we report a novel homozygousRIPK1variant in a boy with immunodeficiency and chronic enteropathy. Our patient exhibited severe motor delay and mild intellectual disability, which were previously unknown. The present results are expected to deepen the current understanding of clinical features based onRIPK1abnormalities.