Unknown

Dataset Information

0

TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome.


ABSTRACT: A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7. Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified 2 additional TGFB2 mutations. TGFB2 encodes transforming growth factor (TGF)-?2, and the mutations are predicted to cause haploinsufficiency for TGFB2; however, aortic tissue from cases paradoxically shows increased TGF-?2 expression and immunostaining. Thus, haploinsufficiency for TGFB2 predisposes to thoracic aortic disease, suggesting that the initial pathway driving disease is decreased cellular TGF-?2 levels leading to a secondary increase in TGF-?2 production in the diseased aorta.

SUBMITTER: Boileau C 

PROVIDER: S-EPMC4033668 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7. Sanger  ...[more]

Similar Datasets

| S-EPMC4873375 | biostudies-literature
| S-EPMC2958900 | biostudies-literature
| S-EPMC4767350 | biostudies-literature
| S-EPMC4839295 | biostudies-literature
| S-EPMC8670144 | biostudies-literature
| S-EPMC5985335 | biostudies-literature
| S-EPMC8421937 | biostudies-literature
| S-EPMC3738837 | biostudies-literature
| S-EPMC3020128 | biostudies-literature
| S-EPMC6777456 | biostudies-literature