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

Dianna M. Milewicz, John R. Østergaard, Leena M. Ala-Kokko, Nadia Khan, Dorothy K. Grange, Roberto Mendoza-Londono, Timothy J. Bradley, Ann Haskins Olney, Lesley Adès, Joseph F. Maher, Dongchuan Guo, L. Maximilian Buja, Dong Kim, James C. Hyland, Ellen S. Regalado

Research output: Contribution to journalArticlepeer-review

158 Scopus citations


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.

Original languageEnglish
Pages (from-to)2437-2443
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume152 A
Issue number10
StatePublished - Oct 2010


  • ACTA2
  • Alpha-actin
  • Congenital mydriasis
  • Moyamoya disease
  • Smooth muscle cell
  • Thoracic aortic aneurysm


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