Cong Yan, Hu Lin, Wu Ke
Department of Rehabilitation, Yiwu Maternal and Child Health Care Hospital, Yiwu, Zhejiang 322000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Sep 10;38(9):884-886. doi: 10.3760/cma.j.cn511374-20200615-00438.
To explore the genetic basis for a pedigree affected with familial adenomatous polyposis (FAP).
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.
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).
The c.532-1G>A variant of the APC gene probably underlay the pathogenesis of FAP in this pedigree.
探究一个患有家族性腺瘤性息肉病（FAP）家系的遗传基础。
先证者有便血复发症状，通过内镜检查、病理检查及家族史被诊断为FAP。对其进行二代测序以检测基因变异。通过对其家系成员进行桑格测序验证疑似变异。
发现先证者、其母亲和兄弟携带APC基因的杂合c.532-1G>A变异，这可能导致mRNA异常剪接，产生截短蛋白，可能失去其正常功能并促进肿瘤发生。根据美国医学遗传学与基因组学学会的标准和指南，APC基因的c.532-1G>A变异被预测为致病的（PVS1+PP1+PP4+PP5）。
APC基因的c.532-1G>A变异可能是该家系FAP发病机制的基础。
