转甲状腺素蛋白淀粉样变心肌病一家系遗传学分析

Genetic analysis of a pedigree of transthyretin amyloid cardiomyopathy

目的:探讨转甲状腺素蛋白淀粉样变心肌病(ATTR-CM)的遗传学特征。方法:对1例以心肌肥厚所致心力衰竭为主要临床特征的ATTR-CM先证者的临床表型进行分析,通过高通量测序分析转甲状腺素蛋白(TTR)基因突变情况并进行Sanger测序验证。结果:先证者发病年龄较早,临床症状复杂。先证者及其妹妹、侄子、女儿4人存在TTR基因c.A163G(p.Lys55Glu)杂合突变。结论:本研究发现了TTR基因c.A163G(p.Lys55Glu)突变导致的ATTR-CM,异常TTR沉积主要累及心脏,症状复杂且不典型。

Aim:To investigate the genetic features of transthyretin amyloid cardiomyopathy(ATTR-CM).Methods:Clinical phenotypes of a case of ATTR-CM with preexisting heart failure due to myocardial hypertrophy as the main clinical feature were analyzed.Mutations in the transthyretin(TTR)gene in this pedigree were analyzed and genetically validated by Sanger sequencing validation.Results:The proband had an early onset age and complicated clinical symptoms.Gene sequencing results showed that the proband and his sister,nephew,daughter had heterozygous mutation of TTR gene c.A163G(p.Lys55Glu).Conclusion:This study discovered the ATTR-CM caused by TTR gene c.A163G(p.Lys55Glu)mutation.Abnormal TTR deposition mainly affects the heart,with complex and atypical symptoms.