一个颈动脉体瘤家系的SDHD基因变异研究

Identification of SDHD c.170-1G>T variant in pedigree affected with carotid body tumor

目的对1个颈动脉体瘤家系进行变异检测,明确其病因。方法对家系成员进行查体、彩超检查、CT扫描,对先证者进行外显子组测序,再用Sanger测序进行验证,对候选变异进行功能预测,并在家系成员中进行验证。结果先证者携带SDHD基因第3外显子剪接区c.170-1G>T杂合变异,15个家系成员携带致病变异,其中6人已死于心脑血管病,现存9人均已发生颈动脉体瘤、高血压。本家系符合常染色体显性遗传规律。结论SDHD基因c.170-1G>T杂合变异可能是导致本家系发病的原因,颈动脉体瘤患者除了常规临床检查还应进行基因诊断。

Objective To carry out genetic testing for a pedigree affected with carotid body tumor(CBT).Methods Members of the pedigree were enrolled and underwent physical examination,ultrasonography and CT scan.Genomic DNA of the proband was extracted from peripheral blood sample and subjected to exome sequencing.Candidate variants were predicted using bioinformatic tools and verified among members from his pedigree.Results A c.170-1G>T splicing variant of the SDHD gene was detected in 15 individuals from the pedigree.Physical examination and imaging confirmed that 9 of them had CBT and hypertension,while the remaining 6 died of cardiovascular and cerebrovascular diseases.Conclusion The c.170-1G>T variant of the SDHD gene probably underlies the CBT in this pedigree.Genetic testing should be considered for CBT patients with CBT in addition to conventional clinical examination.