Gut Liver.
2015 Nov;9(6):767-775. 10.5009/gnl15176.
Is Whole Exome Sequencing Clinically Practical in the Management of Pediatric Crohn's Disease?
- Affiliations
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- 1Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
- 2Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea. kysong@amc.seoul.kr
- 3Department of Pediatrics, GangNeung Asan Hospital, Gangneung, Korea.
- 4Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
- 5Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
- 6Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
- 7Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
- 8Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
- KMID: 2377935
- DOI: http://doi.org/10.5009/gnl15176
Abstract
- BACKGROUND/AIMS
The aim of this study was to identify the profile of rare variants associated with Crohn's disease (CD) using whole exome sequencing (WES) analysis of Korean children with CD and to evaluate whether genetic profiles could provide information during medical decision making.
METHODS
DNA samples from 18 control individuals and 22 patients with infantile, very-early and early onset CD of severe phenotype were used for WES. Genes were filtered using panels of inflammatory bowel disease (IBD)-associated genes and genes of primary immunodeficiency (PID) and monogenic IBD.
RESULTS
Eighty-one IBD-associated variants and 35 variants in PID genes were revealed by WES. The most frequently occurring variants were carried by nine (41%) and four (18.2%) CD probands and were ATG16L2 (rs11235604) and IL17REL (rs142430606), respectively. Twenty-four IBD-associated variants and 10 PID variants were predicted to be deleterious and were identified in the heterozygous state. However, their functions were unknown with the exception of a novel p.Q111X variant in XIAP (X chromosome) of a male proband.
CONCLUSIONS
The presence of many rare variants of unknown significance limits the clinical applicability of WES for individual CD patients. However, WES in children may be beneficial for distinguishing CD secondary to PID.
MeSH Terms
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Asian Continental Ancestry Group/genetics
Carrier Proteins/genetics
Child
Child, Preschool
Crohn Disease/*genetics
*Exome
Female
Genetic Predisposition to Disease
*Genetic Variation
Humans
Immunologic Deficiency Syndromes/genetics
Infant
Male
Phenotype
Receptors, Interleukin-17/genetics
Republic of Korea
Sequence Analysis, DNA/*methods
X-Linked Inhibitor of Apoptosis Protein/genetics
Carrier Proteins
Receptors, Interleukin-17
X-Linked Inhibitor of Apoptosis Protein
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