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. 2020 Sep;98(3):261-273.
doi: 10.1111/cge.13801. Epub 2020 Aug 4.

Fetal megacystis-microcolon: Genetic mutational spectrum and identification of PDCL3 as a novel candidate gene

Clarisse Billon  1   2 , Arnaud Molin  3 , Céline Poirsier  4 , Alix Clemenson  5 , Coralie Dauge  6 , Maude Grelet  7 , Sabine Sigaudy  7 , Sophie Patrier  8 , Alice Goldenberg  9 , Valérie Layet  10 , Julia Tantau  1 , Clémence Fleury  11 , Agnès Liard  12 , Alain Diguet  13 , Radia Fritih  14 , Eric Verspyck  15 , John Rendu  16 , Lucile Boutaud  1   17 , Aude Tessier  1 , Sophie Thomas  17 , Ferechté Razavi  1 , Amale Achaiaa  1 , Nadia Elkhartoufi  1 , Leila Hakkakian  1 , Eglantine Magnin  1 , Christine Bôle-Feysot  18 , Cécile Masson  19 , Yves Ville  20 , Philippe Roth  20 , Fabienne Prieur  21 , Bettina Bessieres  1 , Maryse Bonniere  1 , Tania Attie-Bitach  1   17
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Fetal megacystis-microcolon: Genetic mutational spectrum and identification of PDCL3 as a novel candidate gene

Clarisse Billon et al. Clin Genet. 2020 Sep.

Abstract

Megacystis-microcolon-intestinal-hypoperistalsis syndrome (MMIHS) is a severe congenital visceral myopathy characterized by an abdominal distension due to a large non-obstructed urinary bladder, a microcolon and intestinal hypo- or aperistalsis. Most of the patients described to date carry a sporadic heterozygous variant in ACTG2. More recently, recessive forms have been reported and mutations in MYH11, LMOD1, MYLK and MYL9 have been described at the molecular level. In the present report, we describe five patients carrying a recurrent heterozygous variant in ACTG2. Exome sequencing performed in four families allowed us to identify the genetic cause in three. In two families, we identified variants in MMIHS causal genes, respectively a nonsense homozygous variant in MYH11 and a previously described homozygous deletion in MYL9. Finally, we identified compound heterozygous variants in a novel candidate gene, PDCL3, c.[143_144del];[380G>A], p.[(Tyr48Ter)];[(Cys127Tyr)]. After cDNA analysis, a complete absence of PDLC3 expression was observed in affected individuals, indicating that both mutated transcripts were unstable and prone to mediated mRNA decay. PDCL3 encodes a protein involved in the folding of actin, a key step in thin filament formation. Presumably, loss-of-function of this protein affects the contractility of smooth muscle tissues, making PDCL3 an excellent candidate gene for autosomal recessive forms of MMIHS.

Keywords: MMIHS; PDCL3; fetus; phosducin-like protein; smooth muscle.

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References

REFERENCES

    1. Puri P, Shinkai M. Megacystis microcolon intestinal hypoperistalsis syndrome. Semin Pediatr Surg. 2005;14(1):58-63.
    1. Muller F, Dreux S, Vaast P, et al. Prenatal diagnosis of megacystis-microcolon-intestinal hypoperistalsis syndrome: contribution of amniotic fluid digestive enzyme assay and fetal urinalysis. Prenat Diagn. 2005;25(3):203-209. https://doi.org/10.1002/pd.1088.
    1. Gosemann J-H, Puri P. Megacystis microcolon intestinal hypoperistalsis syndrome: systematic review of outcome. Pediatr Surg Int. 2011;27(10):1041-1046. https://doi.org/10.1007/s00383-011-2954-9.
    1. Thorson W, Diaz-Horta O, Foster J, et al. De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis. Hum Genet. 2014;133(6):737-742. https://doi.org/10.1007/s00439-013-1406-0.
    1. Wangler MF, Gonzaga-Jauregui C, Gambin T, et al. Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2) gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome. PLoS Genet. 2014;10(3):e1004258. https://doi.org/10.1371/journal.pgen.1004258.

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