Clinical Practice Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2018; 24(9): 1035-1045
Published online Mar 7, 2018. doi: 10.3748/wjg.v24.i9.1035
Phenotypic and genotypic characterization of inflammatory bowel disease in children under six years of age in China
You-Hong Fang, You-You Luo, Jin-Dan Yu, Jin-Gan Lou, Jie Chen
You-Hong Fang, You-You Luo, Jin-Dan Yu, Jin-Gan Lou, Jie Chen, Department of Gastroenterology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
Author contributions: Chen J, Fang YH and Luo YY designed the research; Fang YH, Luo YY, Yu JD, Lou JG and Chen J performed the research; Fang YH analyzed the data; Fang YH and Chen J wrote the paper.
Supported by Zhejiang Province Medical Platform Backbone, No. 2017KY436.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Children’s Hospital of Zhejiang University School of Medicine.
Conflict-of-interest statement: The authors have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jie Chen, MD, Attending Doctor, Chief Doctor, Department of Gastroenterology, Children’s Hospital, Zhejiang University School of Medicine, 3333 Bin Sheng Road, Hangzhou 310052, Zhejiang Province, China. hzcjie@zju.edu.cn
Telephone: +86-571-87061007
Received: December 12, 2017
Peer-review started: December 12, 2017
First decision: January 18, 2018
Revised: January 31, 2018
Accepted: February 8, 2018
Article in press: February 8, 2018
Published online: March 7, 2018
Abstract
AIM

To analyze clinical differences between monogenic and nonmonogenic very-early-onset inflammatory bowel disease (VEO-IBD) and to characterize monogenic IBD phenotypically and genotypically via genetic testing.

METHODS

A retrospective analysis of children aged 0 to 6 years diagnosed with VEO-IBD in a tertiary hospital in southern China from 2005 to 2017 was performed. Clinical data for VEO-IBD patients were collected, and genetic characteristics were analyzed using whole exome sequencing or target gene panel sequencing.

RESULTS

A total of 54 VEO-IBD patients were included in this study. A diagnosis of Crohn’s disease (CD) or CD-like intestinal manifestations accounted for 72.2% of the VEO-IBD cases. Nine patients (16.7%) were identified by genetic testing as having monogenic IBD. The median age of diagnosis in the monogenic group was younger than that of the nonmonogenic IBD group, at 18 mo (interquartile range (IQR): 4 to 78) and 43.5 mo (IQR: 3 to 173), respectively; the P-value was 0.021. The incidence of perianal disease in the monogenic group was higher than that in the nonmonogenic group (P = 0.001). However, there were no significant differences between weight-for-age and height-for-age Z-scores between the two groups, and similar laboratory results were obtained for the two groups. Five patients were found to have IL10 receptor mutation, two patients had chronic granulomatous disease, one patient had common variable immunodeficiency disease, and one patient had X-linked inhibitor of apoptosis protein deficiency.

CONCLUSION

A high proportion of monogenic IBD was observed in the VEO-IBD group, especially with disease onset before the age of 6 mo. Monogenic IBD and nonmonogenic IBD exhibited similar clinical features. Furthermore, next-generation sequencing played an important role in the diagnosis of monogenic IBD, and IL10 receptor mutation was predominant in this cohort.

Keywords: Monogenic, Very-early-onset inflammatory bowel disease, Primary immunodeficiency diseases, IL10, IL10R

Core tip: This study is the largest study to analyze clinical differences between monogenic and nonmonogenic very-early-onset inflammatory bowel disease (VEO-IBD) in China. Moreover, we characterized monogenic IBD phenotypically and genotypically through genetic testing (whole exome sequencing and targeted gene panel sequencing). We found a high proportion of monogenic IBD in the VEO-IBD group, with the most common monogenic IBD being IL10R mutation. Monogenic IBD and nonmonogenic IBD showed similar clinical features. Next-generation sequencing played an important role in the diagnosis of monogenic IBD.