临床表现不典型极早发型炎症性肠病28型患儿1例的临床与遗传学分析

Clinical and genetic analysis of a very early-onset inflammatory bowel disease type 28 child with atypical clinical manifestation

目的探讨1例临床表现不典型极早发型炎症性肠病(VEO-IBD)28型患儿的临床特征与遗传学病因。方法选取2021年11月5日于山东大学附属儿童医院新生儿科就诊的1例临床表现不典型VEO-IBD28型患儿为研究对象。收集患儿临床资料,采集患儿及其父母外周静脉血样,应用高通量测序对患儿进行基因检测,采用Sanger测序进行候选变异家系验证,并进行生物信息学分析。结果患儿为50 d龄男性,具有支气管炎、溃疡性口炎、湿疹、大便略稀等临床表现。高通量测序结果提示患儿IL-10RA基因存在c.299T>G(p.V100G)与c.301C>T(p.R101W)复合杂合变异,Sanger测序结果显示患儿父亲IL-10RA基因存在c.299T>G(p.V100G)杂合变异,患儿母亲IL-10RA基因存在c.301C>T(p.R101W)杂合变异。IL-10RA基因c.299T>G与c.301C>T变异在HGMD数据库中均已见报道;经gnomAD、1000 Genomes、ExAC及ESP6500等数据库检索,c.299T>G变异未见收录,c.301C>T变异已见收录且为低频变异;经SIFT、PolyPhen-2及Mutation Taster等在线软件分析,c.299T>G与c.301C>T变异均被预测为可能有害性变异;根据美国医学遗传学与基因组学学会(ACMG)相关指南,c.299T>G与c.301C>T变异均被评级为致病性变异(PS3+PM2Supporting+PP3)。结论IL-10RA基因c.299T>G与c.301C>T变异可能为该VEO-IBD28型患儿的遗传学病因,进一步拓展了IL-10RA基因变异所致VEO-IBD28型患儿表型谱,为该病患儿临床诊断提供参考依据。

Objective To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease(VEO-IBD)type 28 child with atypical clinical manifestations.Methods A VEO-IBD type 28 child with atypical clinical manifestation admitted to the Department of Neonatology,Children′s Hospital Affiliated to Shandong University on November 5,2021 was selected as the study subject.Clinical data of the child was collected.Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing.Candidate variants were verified by Sanger sequencing and bioinformatic analysis.Results The child,a 50-day old male,had manifested bronchitis,ulcerative stomatitis,eczema and slightly loose stool.High-throughput sequencing revealed that he harbored compound heterozygous variants of the IL-10RA gene,namely c.299T>G(p.V100G)and c.301C>T(p.R101W),which were inherited from his father and mother,respectively.Bioinformatic analysis showed that both variants have been recorded in the HGMD database,though the c.299T>G variant has not been included in the gnomAD,1000 Genomes,ExAC and ESP6500 databases,while the c.301C>T variant has a low population frequency.Both variants were predicted to be deleterious by the online software including SIFT,PolyPhen-2 and Mutation Taster.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),both variants were predicted to be pathogenic(PS3+PM2_Supporting+PP3).Conclusion The c.299T>G and c.301C>T variants of theIL-10RA gene probably underlay the VEO-IBD type 28 in this child.Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.