一个家族性腺瘤性息肉病家系的APC基因变异分析

Analysis of APC gene variants in a pedigree affected with familial adenomatous polyposis

目的对1个家族性腺瘤性息肉病家系成员进行基因变异分析,明确其可能的致病原因。方法应用二代测序技术对先证者进行基因检测,应用Sanger测序对先证者及家系成员进行变异验证。结果先证者及其母亲和哥哥APC基因存在c.532-1G>A杂合变异,该变异为剪接位点变异,会导致APC基因mRNA的异常剪接,造成APC蛋白截短,影响正常功能发挥,促进肿瘤发生。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,APC基因c.532-1G>A变异判定为致病性变异(PVS1+PP1+PP4+PP5)。结论APC基因c.532-1G>A变异可能是本家系家族性腺瘤性息肉病的遗传学病因。

Objective To explore the genetic basis for a pedigree affected with familial adenomatous polyposis(FAP).Methods The proband,with recurrence of blood in the stool,was diagnosed with FAP by endoscopy,pathological examination and a family history.She was subjected to next generation sequencing to detect genetic variant.Suspected variant was verified by Sanger sequencing of members from her pedigree.Results The proband,her mother and brother were found to carry a heterozygous c.532-1G>A variant of the APC gene,which may lead to aberrant splicing of mRNA resulting in a truncated protein,which may lose its normal function and promote the tumorigenesis.Based on the American College of Medical Genetics and Genomics standards and guidelines,c.532-1G>A variant of APC gene was predicted to be pathogenic(PVS1+PP1+PP4+PP5).Conclusion The c.532-1G>A variant of the APC gene probably underlay the pathogenesis of FAP in this pedigree.