title: Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution.
abstract: Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin γ-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolon-intestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Biomedical Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Joakim
authors.identifier: http://orcid.org/0000-0003-4185-7409
authors.initials: J
authors.lastname: Klar
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Biomedical Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Doroteya
authors.identifier: http://orcid.org/0000-0001-6452-2199
authors.initials: D
authors.lastname: Raykova
authors.affiliation: Department of Womens and Childrens Health, Uppsala University, Uppsala, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Gustafson
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Biomedical Centre, Uppsala University, Uppsala, Sweden.|Department of Biology, Faculty of Humanities and Natural Sciences, University of Presov, Presov, Slovak Republic.
authors.forename: Iveta
authors.initials: I
authors.lastname: Tóthová
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Biomedical Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Adam
authors.initials: A
authors.lastname: Ameur
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Biomedical Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Alkwin
authors.initials: A
authors.lastname: Wanders
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Biomedical Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
mesh_terms: D000199:Actins / Q000737:chemistry / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D004386:Duodenum / Q000002:abnormalities*; D005260:Female; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D001743:Urinary Bladder / Q000002:abnormalities*
chemical_list: C579475:ACTG2 protein, human; D000199:Actins