De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis

Willa Thorson, Oscar Diaz-Horta, Joseph Foster, Michail Spiliopoulos, Ruben A. Quintero, Amjad Farooq, Susan Blanton, Mustafa Tekin

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is characterized by prenatal-onset distended urinary bladder with functional intestinal obstruction, requiring extensive surgical intervention for survival. While it is believed to be an autosomal recessive disorder, most cases are sporadic. Through whole-exome sequencing in a child with MMIHS, we identified a de novo mutation, p.R178L, in the gene encoding the smooth muscle gamma-2 actin, ACTG2. We subsequently detected another de novo ACTG2 mutation, p.R178C, in an additional child with MMIHS. Actg2 transcripts were primarily found in murine urinary bladder and intestinal tissues. Structural analysis and functional experiments suggested that both ACTG2 mutants interfere with proper polymerization of ACTG2 into thin filaments, leading to impaired contractility of the smooth muscle. In conclusion, our study suggests a pathogenic mechanism for MMIHS by identifying causative ACTG2 mutations.

Original languageEnglish (US)
Pages (from-to)737-742
Number of pages6
JournalHuman Genetics
Volume133
Issue number6
DOIs
StatePublished - Jun 2014

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis'. Together they form a unique fingerprint.

  • Cite this