Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution.

Klar J, Raykova D, Gustafson E, Tóthová I, Ameur A, Wanders A, Dahl N

Eur. J. Hum. Genet. 23 (12) 1679-1683 [2015-12-00; online 2015-03-18]

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.

NGI Uppsala (Uppsala Genome Center)

National Genomics Infrastructure

PubMed 25782675

DOI 10.1038/ejhg.2015.49

Crossref 10.1038/ejhg.2015.49

pii: ejhg201549
pmc: PMC4795199

Publications 9.5.0