A homozygous loss-of-function variant in MYH11 in a case with megacystis-microcolon-intestinal hypoperistalsis syndrome

Julie Gauthier, Bouchra Ouled Amar Bencheikh, Fadi F. Hamdan, Steven M. Harrison, Linda A. Baker, Françoise Couture, Isabelle Thiffault, Reda Ouazzani, Mark E. Samuels, Grant A. Mitchell, Guy A. Rouleau, Jacques L. Michaud, Jean François Soucy

Research output: Contribution to journalReview article

39 Scopus citations

Abstract

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is characterized by marked dilatation of the bladder and microcolon and decreased intestinal peristalsis. Recent studies indicate that heterozygous variants in ACTG2, which codes for a smooth muscle actin, cause MMIHS. However, such variants do not explain MMIHS cases that show an autosomal recessive mode of inheritance. We performed exome sequencing in a newborn with MMIHS and prune belly phenotype whose parents are consanguineous and identified a homozygous variant (c.3598A>T: p.Lys1200Ter) in MYH11, which codes for the smooth muscle myosin heavy chain. Previous studies showed that loss of Myh11 function in mice causes a bladder and intestinal phenotype that is highly reminiscent of MMIHS. All together, these observations strongly suggest that loss-of-function variants in MYH11 cause MMIHS. The documentation of variants in ACTG2 and MYH11 thus points to the involvement of the contractile apparatus of the smooth muscle in MMIHS. Interestingly, dominant-negative variants in MYH11 have previously been shown to cause thoracic aortic aneurism and dilatation. Different mechanisms of MYH11 disruption may thus lead to distinct patterns of smooth muscle dysfunction.

Original languageEnglish (US)
Pages (from-to)1266-1268
Number of pages3
JournalEuropean Journal of Human Genetics
Volume23
Issue number9
DOIs
StatePublished - Sep 14 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Gauthier, J., Ouled Amar Bencheikh, B., Hamdan, F. F., Harrison, S. M., Baker, L. A., Couture, F., Thiffault, I., Ouazzani, R., Samuels, M. E., Mitchell, G. A., Rouleau, G. A., Michaud, J. L., & Soucy, J. F. (2015). A homozygous loss-of-function variant in MYH11 in a case with megacystis-microcolon-intestinal hypoperistalsis syndrome. European Journal of Human Genetics, 23(9), 1266-1268. https://doi.org/10.1038/ejhg.2014.256