一个结节性硬化症家系的临床特征及基因突变分析

Analysis of clinical features and genetic variants in a Chinese pedigree affected with tuberous sclerosis

目的分析一个中国人结节性硬化症家系的临床特征,并探讨其发病的分子机制。方法收集先证者及其家系成员的临床资料,采用全外显子组测序技术对先证者外周血DNA的TSC1和TSC2基因变异进行鉴定。经生物信息学分析后,对发现的潜在致病变异采用Sanger测序法对父母进行验证。结果先证者及其母亲均携带TSC2基因新的c.4183C>T(p.Q1395X)杂合变异,生物信息学分析提示该变异为潜在的致病变异。先证者母亲同样诊断为结节性硬化症,但症状轻于患者。另外4名未患病的家系成员未发现上述突变。结论TSC2基因新的c.4183C>T(p.Q1395X)杂合变异可能是该家系的致病原因。上述发现扩大了TSC2基因的突变谱。先证者症状重于其母亲考虑与表型异质性有关。

Objective To analyze the clinical features of a Chinese pedigree affected with tuberculosis sclerosis and explore its molecular pathogenesis.Methods Clinical data of the proband and members of his pedigree were collected.Whole exome sequencing was carried out to detect variants of the TSC1 and TSC2 genes.Candidate variants was verifed by Sanger sequencing and bioinformatic analysis.Results The proband and his mother,who also had mild features of tuberous sclerosis,were found to harbor a novel heterozygous c.4183C>T(p.Q1395X)variant of the TSC2 gene,which was absent in the 4 healthy relatives.Bioinformatic analysis suggested the variant to be likely pathogenic.Conclusion The heterozygous c.4183C>T(p.Q1395X)variant of the TSC2 gene probably underlay the disease in this pedigree.Above finding has expanded the spectrum of TSC2 gene variants.The more severe symptoms in the proband may be attributed to phenotypic heterogeneity of this disease.