title: A Synonymous Variant in IL10RA Affects RNA Splicing in Paediatric Patients with Refractory Inflammatory Bowel Disease.
abstract: Interleukin-10 receptor [IL10R] mutations are associated with severe childhood inflammatory bowel disease [IBD]. Two unrelated patients who died of very early-onset severe IBD and sepsis were identified as harbouring the same compound heterozygous mutations in IL10RA [p.R101W; p.T179T]. A third patient was found to be homozygous for p.T179T. The missense change of p.R101W has been reported. The synonymous change of p.T179T, with a minor allele frequency of 0.035% in the population, was novel. The p.T179T mutation was located before the 5' splice donor site, leading to exon skipping and out-of-frame fusion of exons 3 and 5, causing altered STAT3 phosphorylation in IL10-induced peripheral blood mononuclear cells. The patient developed colitis at 6 years of age, the oldest reported age of onset among patients with IL10RA mutations, and did not suffer from perianal disease. We report three paediatric patients with a rare, synonymous p.T179T variant causing a splicing error in IL10RA.
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Seak Hee
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Baek
authors.affiliation: Human Genetics Group, Genome Institute of Singapore, Singapore.
authors.forename: Herty
authors.initials: H
authors.lastname: Liany
authors.affiliation: Human Genetics Group, Genome Institute of Singapore, Singapore.
authors.forename: Jia Nee
authors.initials: JN
authors.lastname: Foo
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kyung Mo
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Stephen Chang-Oh
authors.initials: SC
authors.lastname: Yang
authors.affiliation: Human Genetics Group, Genome Institute of Singapore, Singapore.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea kysong@amc.seoul.kr.
authors.forename: Kyuyoung
authors.initials: K
authors.lastname: Song
mesh_terms: D017398:Alternative Splicing; D002648:Child; D003424:Crohn Disease / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense / Q000235:genetics* / Q000502:physiology; D053701:Receptors, Interleukin-10 / Q000235:genetics* / Q000502:physiology
chemical_list: D053701:Receptors, Interleukin-10
keywords: Crohn’s disease; IL10RA; exome sequencing; synonymous variant