Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thoracic aortic aneurysm (TAA) is a genetically mediated disease with variable age of onset. In the pediatric age range, nonsyndromic TAA frequently has a milder course than syndromic forms of TAA, such as Marfan syndrome or Loeys-Dietz syndrome. Herein, we describe 17-year-old identical twin brothers with severe progressive TAA due to a novel de novo ACTA2 mutation. Interestingly, both boys were diagnosed at age 11 with congenital mydriasis, a recently recognized manifestation of some ACTA2 mutations due to smooth muscle dysfunction. One of the brothers presented with acute-onset lower back pain that was identified as dissection of an abdominal aortic aneurysm. Imaging of the chest at this time showed severe fusiform TAA. Cardiac imaging in his twin showed similar TAA, but no abdominal aortic aneurysm. Both brothers underwent valve-sparing aortic root replacement, but have had progressive aortic disease with recurrent dissection requiring multiple surgeries. This case emphasizes the importance of identifying physical stigmata of smooth muscle dysfunction, such as mydriasis, as potential markers for associated aortopathy and vascular diseases.
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PMID:Twins with progressive thoracic aortic aneurysm, recurrent dissection and ACTA2 mutation. 2522 39

Genetic causes for abdominal aortic aneurysm (AAA) have not been identified and the role of genes associated with familial thoracic aneurysms in AAA has not been explored. We analyzed nine genes associated with familial thoracic aortic aneurysms, the vascular Ehlers-Danlos gene COL3A1 and the MTHFR p.Ala222Val variant in 155 AAA patients. The thoracic aneurysm genes selected for this study were the transforming growth factor-beta pathway genes EFEMP2, FBN1, SMAD3, TGBF2, TGFBR1, TGFBR2, and the smooth muscle cells genes ACTA2, MYH11 and MYLK. Sanger sequencing of all coding exons and exon-intron boundaries of these genes was performed. Patients with at least one first-degree relative with an aortic aneurysm were classified as familial AAA (n = 99), the others as sporadic AAA. We found 47 different rare heterozygous variants in eight genes: two pathogenic, one likely pathogenic, twenty-one variants of unknown significance (VUS) and twenty-three unlikely pathogenic variants. In familial AAA we found one pathogenic and segregating variant (COL3A1 p.Arg491X), one likely pathogenic and segregating (MYH11 p.Arg254Cys), and fifteen VUS. In sporadic patients we found one pathogenic (TGFBR2 p.Ile525Phefs*18) and seven VUS. Thirteen patients had two or more variants. These results show a previously unknown association and overlapping genetic defects between AAA and familial thoracic aneurysms, indicating that genetic testing may help to identify the cause of familial and sporadic AAA. In this view, genetic testing of these genes specifically or in a genome-wide approach may help to identify the cause of familial and sporadic AAA.
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PMID:First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm. 2601 85