Is Whole Exome Sequencing Clinically Practical in the Management of Pediatric Crohn's Disease?
OBJECTIVE
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.
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Seak Hee
SH
Oh
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Jiwon
J
Baek
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Kyung Mo
KM
Kim
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Eun-Ju
EJ
Lee
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Yusun
Y
Jung
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Yeoun Joo
YJ
Lee
Department of Pediatrics, GangNeung Asan Hospital, Gangneung, Seoul, Korea.
Hyun-Seung
HS
Jin
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Byong Duk
BD
Ye
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Suk-Kyun
SK
Yang
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Jong-Keuk
JK
Lee
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Eul-Ju
EJ
Seo
Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Hyun Taek
HT
Lim
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Inchul
I
Lee
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Kyuyoung
K
Song
D044466:Asian People / Q000235:genetics; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000235:genetics*; D059472:Exome; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D007223:Infant; D008297:Male; D010641:Phenotype; D053722:Receptors, Interleukin-17 / Q000235:genetics; D056910:Republic of Korea; D017422:Sequence Analysis, DNA / Q000379:methods*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C548677:IL17REL protein, human; D053722:Receptors, Interleukin-17; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human
Child; Crohn disease; Exome sequencing; Primary immunodeficiency; Rare variant