ACTA2基因c.583delC突变导致家族性胸主动脉瘤及夹层的实验研究

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中图分类号：R654.3 文献标志码：ADOI：10.7652/jdyxb202505017

Familial thoracic aortic aneurysm and dissection caused by c.583delC mutation of ACTA2 gene

LI Jinjie¹，ZHANGQuanzeng²，ZHULin1，LIUJiayun1，YANGLiu1 （1.Department of Clinical Laboratory Medicine，Xijing Hospital，Air Force Military Medical University，Xi'an 71oo32；2. Department of Neurology， Xi'an Central Hospital，Xi'an 7loooO，China）

ABSTRACT：ObjectiveTo search for and verify the genetic factors that lead to familial thoracic aortic aneurysm and dissection.MethodsPatients with a family history were screened from clinical cases of thoracic aortic aneurysmand dissction，and their relevant clinical data were collcted.After extracting the whole-genome DNA from the proband's blood samples，gene panel testing was carried out， and first-generation sequencing was used to verify the blood samples of the proband’s immediate andcollateral relatives.Meanwhile，relevant cell experiments were designed.First，the ACTA2-Leu195 ∗ point mutation plasmid was constructed，and then the mutant plasmid and wild-type ACTA2 were transfected into cells through expresion plasmids respectively.After 48 hours，RNA and total protein were extracted，and the expression levels were detected by qPCR and Western bloting，respectively.ResultsThrough high-throughput sequencing，the mutation site of c.583delC in the ACTA2 gene was found，and it was also confirmed that the heterozygous mutation at this site in the family was closely related to familial thoracic aortic aneurysmand dissection.Theresults of cellexperiments showed that the mRNA and proteinexpresion levels in the group transfected with the ACTA2-Leul95 *mutant plasmid were significantly decreased compared with those of the wild type，suggesting that the mutant could not express proteins normally. ConclusionThrough clinical family studies and cel-level experiments，a new mutation site in ACTA2 leading to familial thoracic aortic aneurysm and dissection has been discovered，which provides a new approach for the screening，detection and clinical treatment of familial thoracic aortic aneurysm and dissection.

KEY WORDS：familial thoracic aortic aneurysm and dissction；ACTA 2；gene mutation；abnormal protein expresion

家族性胸主动脉瘤（familialthoracicaorticaneurysmand dissection，FTAAD）是一种罕见的遗传性心血管疾病，通常为常染色体显性遗传]。（剩余11601字）