Transthyretin Cardiac Amyloidosis Caused by Lys55Glu Mutation in TTR Gene:a Pedigree Report and Literature Review
10.3969/j.issn.1000-3614.2024.10.009
- VernacularTitle: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
- Author:
Xiaoyang JI
1
;
Lili XIAO
;
Xintong CAI
;
Zhe ZHENG
;
Xiaofang WANG
;
Youyou DU
;
Lu GAO
Author Information
1. 郑州大学第一附属医院 心血管内科,郑州 450052
- Keywords:
cardiac amyloidosis;
TTR gene;
gene mutation;
clinical phenotype
- From:
Chinese Circulation Journal
2024;39(10):1009-1015
- CountryChina
- Language:Chinese
-
Abstract:
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.
