Oh Seak Hee, Baek Jiwon, Kim Kyung Mo, Lee Eun-Ju, Jung Yusun, Lee Yeoun Joo, Jin Hyun-Seung, Ye Byong Duk, Yang Suk-Kyun, Lee Jong-Keuk, Seo Eul-Ju, Lim Hyun Taek, Lee Inchul, Song Kyuyoung
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Gut Liver. 2015 Nov 23;9(6):767-75. doi: 10.5009/gnl15176.
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.
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.
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.
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.
背景/目的：本研究旨在通过对韩国克罗恩病（CD）患儿进行全外显子组测序（WES）分析，确定与CD相关的罕见变异谱，并评估基因谱是否能在医疗决策过程中提供信息。
将18名对照个体以及22名患有严重表型的婴儿期、极早期和早期发病CD患者的DNA样本用于WES。使用炎症性肠病（IBD）相关基因以及原发性免疫缺陷（PID）和单基因IBD基因筛选基因。
WES揭示了81个IBD相关变异和35个PID基因变异。最常出现的变异分别由9名（41%）和4名（18.2%）CD先证者携带，分别为ATG16L2（rs11235604）和IL17REL（rs142430606）。24个IBD相关变异和10个PID变异被预测为有害变异，并以杂合状态被鉴定出来。然而，除了一名男性先证者XIAP（X染色体）中的一个新的p.Q111X变异外，它们的功能尚不清楚。
许多意义不明的罕见变异的存在限制了WES对个体CD患者的临床适用性。然而，对儿童进行WES可能有助于区分继发于PID的CD。
