全外显子组测序诊断由TCOF1基因变异所致的Treacher-Collins综合征一个家系

Diagnosis of a Chinese pedigree affected with Treacher-Collins syndrome due to a novel variant of TCOF1 gene through whole exome sequencing

目的通过全外显子组测序(WES)探讨1个Treacher-Collins综合征(TCS)家系的遗传学病因。方法回顾性分析2020年2月5日于青岛大学附属妇女儿童医院就诊的1个TCS家系的临床资料,运用WES对先证者进行基因检测,对候选变异进行生物信息学分析,并通过Sanger测序进行家系验证。结果WES检测显示先证者携带TCOF1基因c.3337C>T杂合变异,Sanger测序显示其母亲和弟弟携带同样的杂合变异。依据美国医学遗传学与基因组学学会(ACMG)相关指南,该变异评定为致病性(PVS1+PM2_Supporting+PP4)。结论TCOF1:c.3337C>T可考虑为该TCS家系患病成员的致病原因。

Objective To explore the genetic etiology for a Chinese pedigree affected with Treacher-Collins syndrome(TCS)through whole exome sequencing(WES).Methods A TCS pedigree which was diagnosed at the Women and Children′s Hospital Affiliated to Qingdao University on February 52020 was selected as the study subject.Following collection of clinical data,WES was carried out.Candidate variant was validated through Sanger sequencing and bioinformatic analysis..Results The WES results showed that the proband has harbored a heterozygous c.3337C>T variant of the TCOF1 gene,and Sanger sequencing confirmed that his mother and brother also carried the same variant.Based on guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was predicted as pathogenic(PVS1+PM2_Supporting+PP4).Conclusion The heterozygous c.3337C>T variant of the TCOF1 gene probably underlay the pathogenesis of TCS in this pedigree.