De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction

Am J Med Genet A. 2010 Oct;152A(10):2437-43. doi: 10.1002/ajmg.a.33657.


Smooth muscle cells (SMCs) contract to perform many physiological functions, including regulation of blood flow and pressure in arteries, contraction of the pupils, peristalsis of the gut, and voiding of the bladder. SMC lineage in these organs is characterized by cellular expression of the SMC isoform of α-actin, encoded by the ACTA2 gene. We report here on a unique and de novo mutation in ACTA2, R179H, that causes a syndrome characterized by dysfunction of SMCs throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation, and hypoperistalsis of the gut and pulmonary hypertension.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics*
  • Adolescent
  • Aneurysm, Dissecting / genetics
  • Aneurysm, Dissecting / surgery
  • Animals
  • Aorta / pathology
  • Aortic Aneurysm / genetics*
  • Aortic Aneurysm / pathology
  • Aortic Aneurysm / surgery
  • Cerebrovascular Disorders / genetics*
  • Cerebrovascular Disorders / pathology
  • Child
  • Female
  • Humans
  • Male
  • Mice
  • Muscle, Smooth / pathology*
  • Muscle, Smooth, Vascular / pathology
  • Mutation
  • Mutation, Missense*
  • Vascular Diseases / genetics*
  • Vascular Diseases / surgery


  • ACTA2 protein, human
  • Actins