title: Variants of the ACTG2 gene correlate with degree of severity and presence of megacystis in chronic intestinal pseudo-obstruction.
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.
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Matera
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Rusmini
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Yiran
authors.identifier: 0000-0002-6549-8589
authors.initials: Y
authors.lastname: Guo
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Lerone
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Pathophysiology of Uremia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Duca
authors.affiliation: Pathology Unit, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Nozza
authors.affiliation: Paediatric Surgery Unit, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Mosconi
authors.affiliation: Paediatric Surgery Unit, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Pini Prato
authors.affiliation: Paediatric Surgery Unit, Istituto Giannina Gaslini, Genova, Italy.|DiNOGMI, University of Genova, Genova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Martucciello
authors.affiliation: Gastroenterology and Endoscopy Unit, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Arrigo
authors.initials: A
authors.lastname: Barabino
authors.affiliation: U.O. Pediatria, Ospedale Sacra Famiglia, Erba (CO), Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Morandi
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: De Giorgio
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Stanghellini
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.|DiNOGMI, University of Genova, Genova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.affiliation: Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.|Department of Molecular Medicine, Sapienza University, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000199:Actins / Q000235:genetics*; D002648:Child; D003106:Colon / Q000002:abnormalities* / Q000473:pathology; D017124:Conserved Sequence; D059472:Exome; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007418:Intestinal Pseudo-Obstruction / Q000235:genetics* / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D001743:Urinary Bladder / Q000002:abnormalities* / Q000473:pathology; D055815:Young Adult
chemical_list: C579475:ACTG2 protein, human; D000199:Actins
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