目的:探讨中国家系Cowden综合征(CS)的临床特征和遗传病因。
方法:选取2022年11月在宁德师范学院附属宁德市医院确诊的CS家系作为研究对象。收集临床数据,并对现有成员进行基因检测。对候选变体进行致病性分析。
结果:先证者,一个7岁的男性,被发现患有自闭症和智力障碍。整个外显子组测序显示他有一个c.462_463del(p。F154Lfs25)PTEN基因的变体。先证者35岁的母亲,在我们医院被诊断出患有肺错构瘤,表现为脂肪瘤,结节性甲状腺肿,和腺瘤。Sanger测序证实,她对于c.462_463del也是杂合的(p。F154Lfs25)PTEN基因的变体。没有其他家庭成员携带相同的变体。根据美国医学遗传学和基因组学学院(ACMG)的指南,该变异体被分类为致病性(PVS1+PM2_支持+PM6)。
结论:新发现的c.462_463del(p。F154Lfs*25)PTEN基因的变体可能是该谱系中CS的基础。CS患者发生恶性肿瘤的风险更高。临床医生应该意识到这种情况,并强调对患者的随访。
OBJECTIVE: To explore the clinical features and genetic etiology of a Chinese pedigree affected with Cowden syndrome (CS).
METHODS: A CS pedigree diagnosed in November 2022 at the Ningde Municipal Hospital Affiliated to Ningde Normal University was selected as the study subject. Clinical data were collected, and genetic testing was carried out for available members. Pathogenicity analysis was carried out for the candidate variant.
RESULTS: The proband, a 7-year-old male, was found to have autism and intellectual disability. Whole exome sequencing revealed that he has harbored a c.462_463del (p.F154Lfs25) variant of the PTEN gene. The proband\'s 35-year-old mother, who was diagnosed with pulmonary hamartomas at our hospital, has manifested with lipomas, nodular goiter, and adenomas. Sanger sequencing confirmed that she was also heterozygous for the c.462_463del (p.F154Lfs25) variant of the PTEN gene. No other family members has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PM2_Supporting+PM6).
CONCLUSIONS: The newly discovered c.462_463del (p.F154Lfs*25) variant of the PTEN gene probably underlay the CS in this pedigree. CS patients have higher risk for developing malignant tumors. Clinicians should be aware of this condition and emphasize follow-up of the patients.