Variants of the ACTG2 gene correlate with degree of severity and presence of megacystis in chronic intestinal pseudo-obstruction

Ivana Matera, Marta Rusmini, Yiran Guo, Margherita Lerone, Jiankang Li, Jianguo Zhang, Marco Di Duca, Paolo Nozza, Manuela Mosconi, Alessio Pini Prato, Giuseppe Martucciello, Arrigo Barabino, Francesco Morandi, Roberto de Giorgio, Vincenzo Stanghellini, Roberto Ravazzolo, Marcella Devoto, Hakon Hakonarson, Isabella Ceccherini

Research output: Contribution to journalArticlepeer-review


Chronic intestinal pseudo-obstruction (CIPO) syndromes are heterogeneous gastrointestinal disorders, caused by either neuropathy or myopathy, resulting in compromised peristalsis and intestinal obstruction. CIPO can have a profound impact on quality of life, leading the most severely affected individuals to life-long parenteral nutrition and urinary catheterization. To search for disease causing gene(s), we performed the whole exome sequencing (WES) in both eight sporadic and two familial cases, followed by targeted sequencing in additional CIPO patients. After identifying a heterozygous missense variant in the ACTG2 gene in one of 10 patients undergone WES, targeted Sanger sequencing of this gene allowed to detect heterozygous missense variants in 9 of 23 further patients with either megacystis-microcolon-intestinal hypoperistalsis syndrome or intestinal pseudo-obstruction. Variants thus identified, one of which still unreported, affect highly conserved regions of the ACTG2 gene that encodes a protein crucial for correct enteric muscle contraction. These findings provided evidence for a correlation between the clinical phenotype and genotype at the ACTG2 locus, a first step to improve the diagnosis and prognosis of these severe conditions.European Journal of Human Genetics advance online publication, 27 January 2016; doi:10.1038/ejhg.2015.275.

Original languageEnglish
JournalEuropean Journal of Human Genetics
Publication statusAccepted/In press - Jan 27 2016

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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