Homozygous deletion in MYL9 expands the molecular basis of megacystis-microcolon-intestinal hypoperistalsis syndrome

Eur J Hum Genet. 2018 May;26(5):669-675. doi: 10.1038/s41431-017-0055-5. Epub 2018 Feb 16.


Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a severe disease characterized by functional obstruction in the urinary and gastrointestinal tract. The molecular basis of this condition started to be defined recently, and the genes related to the syndrome (ACTG2-heterozygous variant in sporadic cases; and MYH11 (myosin heavy chain 11), LMOD1 (leiomodin 1) and MYLK (myosin light chain (MLC) kinase)-autosomal recessive inheritance), encode proteins involved in the smooth muscle contraction, supporting a myopathic basis for the disease. In the present article, we described a family with two affected siblings with MMIHS born to consanguineous parents and the molecular investigation performed to define the genetic etiology. Previous whole exome sequencing of the affected child and parents did not identify a candidate gene for the disease in this family, but now we present a reanalysis of the data that led to the identification of a homozygous deletion encompassing the last exon of MYL9 (myosin regulatory light chain 9) in the affected individual. MYL9 gene encodes a regulatory myosin MLC and the phosphorylation of this protein is a crucial step in the contraction process of smooth muscle cell. Despite the absence of human or animal phenotype related to MYL9, a cause-effect relationship between MYL9 and the MMIHS seems biologically plausible. The present study reveals a strong candidate gene for autosomal recessive forms of MMIHS, expanding the molecular basis of this disease and reinforces the myopathic basis of this condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / physiopathology
  • Autoantigens / genetics
  • Calcium-Binding Proteins / genetics
  • Colon / abnormalities*
  • Colon / physiopathology
  • Consanguinity
  • Cytoskeletal Proteins / genetics
  • Exome Sequencing*
  • Female
  • Genetic Predisposition to Disease*
  • Heterozygote
  • Homozygote
  • Humans
  • Infant
  • Intestinal Pseudo-Obstruction / genetics*
  • Intestinal Pseudo-Obstruction / physiopathology
  • Male
  • Myosin Light Chains / genetics*
  • Myosin-Light-Chain Kinase / genetics
  • Pedigree
  • Phenotype
  • Sequence Deletion
  • Siblings
  • Urinary Bladder / abnormalities*
  • Urinary Bladder / physiopathology


  • Autoantigens
  • Calcium-Binding Proteins
  • Cytoskeletal Proteins
  • LMOD1 protein, human
  • MYL9 protein, human
  • Myosin Light Chains
  • MYLK protein, human
  • Myosin-Light-Chain Kinase

Supplementary concepts

  • Megacystis microcolon intestinal hypoperistalsis syndrome