Clinical features of interleukin 10 receptor gene mutations in children with very early-onset inflammatory bowel disease.
OBJECTIVE
In the present study, we studied a cohort of patients with very early onset inflammatory bowel disease (IBD) to determine the frequency of mutations in the interleukin 10 (IL10) receptor genes as a cause of early-onset IBD.


METHODS
Sanger sequencing was performed to determine the presence of IL10 and/or IL10 receptor mutations in 17 patients with a diagnosis of very early onset IBD (disease onset <2 years of age in 15 patients, between 3 and 4 years in the other 2). Mutation screening was performed including all of the coding regions of the IL10, IL10RA, and IL10RB genes. We then compared the follow-up findings of the patients with IL10 receptor mutations in terms of demographic, clinical, laboratory, and treatment response properties with those of patients diagnosed as having very early onset IBD with no mutation.


RESULTS
We identified 3 patients bearing mutations in the IL10 or IL10 receptor genes, including 1 mutation in IL10RB that has been described recently (c.G477A, p.Trp159*) and 2 novel mutations affecting the IL10RA gene (c.T192G, p.Tyr64 and c.T133G, p.Trp45Gly). Collectively, these mutations thus provided genetic etiology for 17.6% of the cohort under investigation. The presence of a family history of IBD and the clinical course of Crohn disease differed between patients with mutations in the IL-10 pathway and those without such mutations. Although perianal fistulas were found in all of the patients with IL10 receptor mutations, they were found in only 14.3% of those without such mutations. The lower values of weight-for-age and height-for-age z scores, necessity for more intensive therapy, achievement of longer periods until remission, and frequent relapses in the patients bearing mutations in the IL10 receptor genes all underlined the severity of the disease and its relatively poor response to treatment.


CONCLUSIONS
In spite of the small number of patients with mutations affecting the IL-10 signaling pathway in our study, in all of the patients with IL10 receptor mutations, the disease onset occurs at an early age, the prognosis is poor, and the response to treatment is insufficient.
*Department of Pediatric Gastroenterology, Hepatology and Nutrition, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey †CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences ‡Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
Omer F
OF
Beser
Cecilia Dominguez
CD
Conde
Nina K
NK
Serwas
Fügen Cullu
FC
Cokugras
Tufan
T
Kutlu
Kaan
K
Boztug
Tulay
T
Erkan
D019943:Amino Acid Substitution; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003424:Crohn Disease / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics* / Q000378:metabolism; D053710:Interleukin-10 Receptor beta Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012003:Rectal Fistula / Q000209:etiology*; D012720:Severity of Illness Index
C508609:IL10 protein, human; C081846:IL10RB protein, human; D053709:Interleukin-10 Receptor alpha Subunit; D053710:Interleukin-10 Receptor beta Subunit; D016753:Interleukin-10