title: TNF receptor-associated periodic fever syndrome caused by sequence alterations in exonic splicing enhancers: comment on the article by Trübenbach et al.
abstract: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), an autosomal disease belonging to human autoinflammatory syndromes, is caused by mutations in Tumor Necrosis Factor Receptor Superfamily Member 1A (TNFRSF1A) gene. Trübenbach and colleagues described a patient with two heterozygotic nucleotide transversions in exon 4 of TNFRSF1A gene: the first is a substitution from guanine to cytosine at position 263 of the nucleotide sequence (c.263 G>C); the second is a substitution from cytosine to adenine at position 264 (c.264 C>A); the two mutations affect the amino acid number 88 of the protein. To date, this was the first report of a double monoallelic mutation in a gene related to autoinflammatory syndromes. Using two web interfaces (ESEfinder and RESCUE-ESE), we provide evidence that the double nucleotide change may affect an exonic splicing enhancer (ESE), a sequence element distinct from the canonical splice sites that are needed for normal splicing. ESEs are short and degenerate sequences found within coding exons and required for efficient splicing and splice site recognition. In order to verify if these changes really affect an ESE, it would be useful to analyze the described index case TNFRSF1A cDNA, because if this analysis will evidence an exon skipping in the TNFRSF1A coding sequence, it would then represent the first mutation in autoinflammatory syndromes demonstrated to be caused by ESE elements alteration.
authors.forename: Davide
authors.initials: D
authors.lastname: Martorana
authors.forename: Tauro Maria
authors.initials: TM
authors.lastname: Neri
mesh_terms: D005091:Exons; D056660:Hereditary Autoinflammatory Diseases / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D012326:RNA Splicing; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human