医学
动脉瘤
外显子组测序
主动脉瘤
移码突变
皮肤色素沉着
外显子组
动脉瘤
胸主动脉
内科学
心脏病学
突变
外科
主动脉
色素沉着
遗传学
皮肤病科
基因
生物
作者
Jin Yugan,Tiange Li,Shaoying Wu,Zhongqiang Liu,Yifei Li
出处
期刊:Cardiology in The Young
[Cambridge University Press]
日期:2023-11-30
卷期号:34 (1): 212-217
标识
DOI:10.1017/s1047951123004122
摘要
Abstract Heritable thoracic aortic aneurysms are complex conditions characterised by the dilation or rupture of the thoracic aorta, often occurring as an autosomal-dominant disorder associated with life-threatening complications. In this case report, we present a de novo variant, MFAP5 c.236_237insA (p.N79Kfs9), which is implicated in the development of inherited thoracic aortic aneurysm. The proband, a 15-year-old male, presented with recurrent cough, dull chest pain, chest distress, vomiting, and reduced activity tolerance, leading to the diagnosis of heritable thoracic aortic aneurysms. Whole-exome sequencing identified a novel heterozygous variant in MFAP5 (NM_003480, c.236_237insA, and p.N79Kfs9). MutationTester and PolyPhen-s predicted this variant to be damaging and disease-causing (probability = 1), while the SFIT score indicated protein damage (0.001). Structural analysis using the AlphaFold Protein structure database revealed that this mutation disrupted the N-linked glycosylation site, resulting in a frameshift, amino acid sequence alteration, and truncation of an essential protein site. To our knowledge, this is the first case report describing a young patient with heritable thoracic aortic aneurysm carrying the novel MFAP5 c.236_237insA (p.N79Kfs*9) variant. This variant represents the third identified mutation site associated with heritable thoracic aortic aneurysm. Given the high mortality and morbidity rates associated with thoracic aortic aneurysms, the prevention of severe and fatal complications is crucial in the clinical management of this condition. Our case highlights the importance of whole-exome sequencing and genetic screening in identifying potential pathogenic or likely pathogenic variants, particularly in early-onset patients with aortic dilation, to inform appropriate management strategies.
科研通智能强力驱动
Strongly Powered by AbleSci AI