一例UBR1基因新变异所致Johanson-Blizzard综合征患儿的分析

Analysis of a child with Johanson-Blizzard syndrome due to novel compound heterozygous variants of UBR1 gene

目的:对一例表现为发育迟缓、营养不良及特殊面容的患儿进行临床检查和遗传学分析。方法:收集患儿的临床资料,对患儿及其父母进行家系全外显子组测序,对候选变异用Sanger测序进行验证。结果:患儿具有特殊面容,包括鼻翼发育不全、头皮缺损和牙齿畸形,并有胰腺外分泌不足导致的反复腹泻。基因测序显示患儿携带UBR1基因c.3167C>G(p.S1056X)和c.1911+14C>G复合杂合变异,分别遗传自其父亲和母亲。生物信息学分析显示c.3167C>G为无义变异,既往未见报道;c.1911+14C>G为已知剪接变异。根据美国医学遗传学与基因组学学会相关指南,两个变异分别判断为致病和疑似致病变异。结论:患儿被确诊为UBR1基因复合杂合变异导致的Johanson-Blizzard综合征。新发现的变异扩展了UBR1基因的变异谱,并为该家系的遗传咨询及再生育指导提供了依据。

Objective To analyze the clinical and genetic characteristics of a boy featuring unexplained developmental delay,malnutrition and distinct facial appearance.Methods Physical examination was carried out for the child.Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA and trio-whole exome sequencing.Candidate variants were verified by Sanger sequencing.Results The patient had facial dysmorphism including nasal alae aplasia,scalp defect and teeth deformities,in addition with recurrent diarrhea due to pancreatic exocrine insufficiency.DNA sequencing revealed that he has harbored compound heterozygous variants of the UBR1 gene,namely c.3167C>G(p.S1056X)and c.1911+14C>G,which were inherited from his father and mother,respectively.Database search has suggested the c.3167C>G to be a novel nonsense variant and c.1911+14C>G a known splicing variant.Based on the guidelines of the American College of Medical Genetics and Genomics,the two variants were predicted to be pathogenic and likely pathogenic,respectively.Conclusion The child was diagnosed with Johanson-Blizzard syndrome due to the compound heterozygous variants of the UBR1 gene.Above finding has enriched the mutational spectrum of the UBR1 gene and provided a basis for genetic counseling for this family.