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Eur J Hum Genet. 2016 Aug;24(8):1211-5. doi: 10.1038/ejhg.2015.275. Epub 2016 Jan 27.

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

Author information

1
U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
2
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
3
BGI-Shenzhen, Shenzhen, China.
4
Laboratory of Pathophysiology of Uremia, Istituto Giannina Gaslini, Genova, Italy.
5
Pathology Unit, Istituto Giannina Gaslini, Genova, Italy.
6
Paediatric Surgery Unit, Istituto Giannina Gaslini, Genova, Italy.
7
DiNOGMI, University of Genova, Genova, Italy.
8
Gastroenterology and Endoscopy Unit, Istituto Giannina Gaslini, Genova, Italy.
9
U.O. Pediatria, Ospedale Sacra Famiglia, Erba (CO), Italy.
10
Department of Medical and Surgical Sciences, University of Bologna, St Orsola-Malpighi Hospital, Bologna, Italy.
11
Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
12
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
13
Department of Molecular Medicine, Sapienza University, Rome, Italy.

Abstract

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.

PMID:
26813947
PMCID:
PMC4970688
DOI:
10.1038/ejhg.2015.275
[Indexed for MEDLINE]
Free PMC Article

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