Open AccessIdentification of novel splice mutation in SMAD3 in two Cypriot families with nonsyndromic thoracic aortic aneurysm. Two case reports
Author(s) -
Keravnou Anna,
Bashiardes Evy,
Barberis Vassilis,
Michailidou Kyriaki,
Soteriou Marinos,
Tanteles George A.,
Cariolou Marios A.
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1378
Subject(s) - proband , medicine , exon , thoracic aortic aneurysm , aneurysm , disease , bicuspid aortic valve , genetic testing , aortic dissection , genetic counseling , mutation , dissection (medical) , splice , aortic aneurysm , index case , genetics , bioinformatics , gene , surgery , biology , aorta
Background Thoracic aortic aneurysm and dissection (TAA/D) represents a potentially lethal disease group characterized by an increased risk of dissection or rupture. Only a small percentage (approximately 30%) of individuals with nonsyndromic familial TAA/D have a pathogenic variant in one of the genes that have been found to be associated with the disease. Methods A targeted sequencing panel and direct sequencing approach were used to identify causative mutations in the index patients and other family members. Results In this study we report two apparently unrelated Cypriot families with nonsyndromic familial TAA/D. The proband A is a female patient diagnosed with TAA/D and intracranial aneurysm and opted for an elective intervention. The proband B is a male patient who was diagnosed with TAA/D and underwent cardiac surgery. Sequencing analysis identified a novel splice site variant (c.871+1G>A) in SMAD3 which is shown to be associated with the disease. Analysis of mRNA from the patient's tissue confirmed aberrant splicing and exon 6 skipping. Conclusion Our findings expand the mutation spectrum of variants that have been shown to be associated with nonsyndromic familial TAA/D. This study demonstrates the importance of a comprehensive clinical and genetic evaluation aiming at early diagnosis and intervention.