Girardelli Martina, Vuch Josef, Tommasini Alberto, Crovella Sergio, Bianco Anna Monica
Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell'Istria 65/1, Trieste 34137, Italy.
Department of Medicine and Surgery and Health, University of Trieste, Piazzale Europa, 1, Trieste 34128, Italy.
Int J Mol Sci. 2014 Mar 3;15(3):3834-41. doi: 10.3390/ijms15033834.
Deregulated immune response to gut microflora in genetically predisposed individuals is typical for inflammatory bowel diseases. It is reasonable to assume that genetic association with the disease will be more pronounced in subjects with early onset than adult onset. The nucleotide-binding oligomerization domain containing-2 gene, commonly involved in multifactorial risk of Crohn's disease, and interleukin 10 receptor genes, associated with rare forms of early onset inflammatory bowel diseases, were sequenced in an early onset patient. We identified a novel variant in the NOD2 gene (c.2857A > G p.K953E) and two already described missense variants in the IL10RA gene (S159G and G351R). The new NOD2 missense variant was examined in silico with two online bioinformatics tools to predict the potentially deleterious effects of the mutation. Although cumulative effect of these variations in the early onset of the disease can be only hypothesized, we demonstrated that family information and in silico studies can be used to predict association with the disease.
在遗传易感性个体中，对肠道微生物群的免疫反应失调是炎症性肠病的典型特征。有理由认为，与该疾病的遗传关联在早发型患者中比成年发病患者更为明显。在一名早发型患者中，对通常与克罗恩病多因素风险相关的含核苷酸结合寡聚化结构域2基因以及与罕见早发型炎症性肠病形式相关的白细胞介素10受体基因进行了测序。我们在NOD2基因中鉴定出一个新变体（c.2857A > G p.K953E），并在IL10RA基因中鉴定出两个已描述的错义变体（S159G和G351R）。使用两种在线生物信息学工具对新的NOD2错义变体进行了计算机模拟检查，以预测该突变的潜在有害影响。虽然这些变异在疾病早发中的累积效应只能进行推测，但我们证明家族信息和计算机模拟研究可用于预测与该疾病的关联。
