Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms.

ABSTRACT:

Rationale

Thoracic aortic aneurysms leading to acute aortic dissections (TAAD) can be inherited in families in an autosomal dominant manner. As part of the spectrum of clinical heterogeneity of familial TAAD, we recently described families with multiple members that had TAAD and intracranial aneurysms or TAAD and intracranial and abdominal aortic aneurysms inherited in an autosomal dominant manner.

Objective

To identify the causative mutation in a large family with autosomal dominant inheritance of TAAD with intracranial and abdominal aortic aneurysms by performing exome sequencing of 2 distantly related individuals with TAAD and identifying shared rare variants.

Methods and results

A novel frame shift mutation, p. N218fs (c.652delA), was identified in the SMAD3 gene

SUBMITTER: Regalado ES 

PROVIDER: S-EPMC4115811 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature