一例TTR基因Lys55Glu突变致转甲状腺素蛋白心脏淀粉样变患者家系报告及文献复习  

Transthyretin Cardiac Amyloidosis Caused by Lys55Glu Mutation in TTR Gene:a Pedigree Report and Literature Review

作　　者：姬晓阳 肖莉丽[1] 蔡欣桐 郑哲 王小芳[1] 杜优优[1] 高路[1] JI Xiaoyang;XIAO Lili;CAI Xintong;ZHENG Zhe;WANG Xiaofang;DU Youyou;GAO Lu(Department of Cardiology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院心血管内科,郑州450052

出　　处：《中国循环杂志》2024年第10期1009-1015,共7页Chinese Circulation Journal

基　　金：河南省自然科学基金优秀青年基金(242300421477)~~。

摘　　要：目的:报道转甲状腺素蛋白心脏淀粉样变(ATTR-CA)TTR致病基因突变新位点,发现潜在患病家系成员,并提供临床诊疗依据。方法:回顾性分析2021年3月就诊于郑州大学第一附属医院心血管内科的1例ATTR-CA患者(先证者)的临床资料,通过高通量测序方法对先证者进行全外显子组测序以检测突变基因,采用Sanger测序法对其家系可疑成员候选致病基因进行验证,并检索和分析国内外相关文献。结果:在该家系5代共51人中,10人(包括先证者)携带TTR基因c.163A>G杂合突变,导致第55位编码氨基酸残基由赖氨酸(Lys)变为谷氨酸(Glu)。此突变导致的ATTR-CA呈常染色体显性遗传,成年早期发病,进展较快,分型属于混合型ATTR-CA。其中5人有轻重不一的临床表现,其余5人因年龄较小尚未出现症状。该家系中7人死亡,除先证者大舅(Ⅱ-1)于65岁死于脑卒中外,余者均在50岁前死于心脏疾病。结论:依据美国医学遗传学与基因组学学会指南,TTR基因Lys55Glu突变被归为ATTR-CA的一个可能致病的变异,此突变位点尚未被文献报道过,本研究有望扩大TTR基因突变谱。Objectives:To report a novel mutation site in the pathogenic gene TTR of transthyretin cardiac amyloidosis(ATTR-CA),and to identify family members at risk,and provide suitable clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical data of the proband with ATTR-CA who visited the Department of Cardiology,the First Affiliated Hospital of Zhengzhou University in March 2021.The proband underwent whole exome sequencing using high-throughput methods to detect mutation genes.Sanger sequencing was used to test candidate pathogenic loci in suspected family members,and relevant literature was reviewed.Results:Among 51 individuals spanning 5 generations in the pedigree,10 family members(including the proband)carried the heterozygous TTR gene c.163A>G mutation,resulting in the amino acid residue at position 55 changing from lysine(Lys)to glutamic acid(Glu).This mutation follows an autosomal dominant inheritance pattern,with early onset in adulthood,rapid progression,and presenting as a mixed-type ATTR-CA.Five mutation carriers had different clinical manifestations,while the remaining 5 mutation carriers,who are at younger age,have not yet shown symptoms.Within the pedigree,7 individuals died(the proband’s uncle[Ⅱ-1]who died from stroke at 65 years old,the rest 6 family members died from heart disease before the age of 50).Conclusions:According to the American College of Medical Genetics and Genomics guidelines,TTR gene Lys55Glu mutation is classified as likely pathogenic,this mutation site has not been reported in the literature before.Present study adds clinical evidence that might broaden the spectrum of TTR mutations.

关 键 词：心脏淀粉样变 TTR基因 基因突变 临床表型 

分 类 号：R54[医药卫生—心血管疾病]