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.
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Acknowledgements
We thank all family members for their cooperation and participation in the study as well as Dr Konstantin Tomanov, Max F Perutz Laboratories, Vienna, Austria, for valuable advice on 3D protein modeling. This work was supported by grants from the Swedish Research Council (K2013-66X-10829-20-3), Uppsala University Hospital, Uppsala University and the Science for Life Laboratory. JK was supported by the Swedish Society for Medical Research.
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Klar, J., Raykova, D., Gustafson, E. et al. Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution. Eur J Hum Genet 23, 1679–1683 (2015). https://doi.org/10.1038/ejhg.2015.49
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DOI: https://doi.org/10.1038/ejhg.2015.49
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