Novel missense mutation in the NOD2 gene in a patient with early onset ulcerative colitis: causal or chance association?

• Published in: International journal of molecular sciences Vol. 15; no. 3; pp. 3834 - 3841
• Main Authors: Girardelli, Martina, Vuch, Josef, Tommasini, Alberto, Crovella, Sergio, Bianco, Anna Monica
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03-03-2014; Molecular Diversity Preservation International (MDPI)
• Subjects: Age of Onset; Amino Acid Sequence; Base Sequence; Child; Colitis, Ulcerative - epidemiology; Colitis, Ulcerative - genetics; Communication; complex disease; Crohn Disease - genetics; digenic heterozygosis; DNA Mutational Analysis; early onset-inflammatory bowel disease; Genetic Predisposition to Disease - genetics; Genetics; Genotype; Humans; IL10R; Immune system; Inflammatory bowel disease; Interleukin-10 Receptor alpha Subunit - genetics; Interleukin-10 Receptor beta Subunit - genetics; Molecular Sequence Data; Mutation, Missense; NOD2; Nod2 Signaling Adaptor Protein - genetics; Polymorphism, Single Nucleotide; Risk Factors; Sequence Homology, Amino Acid
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.