Browsing by Author "Přistoupilová, A."

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    Mutations in ANTXR1 cause GAPO syndrome
    (University of Chicago Press, 2013) Stránecký, V.; Hoischen, A.; Hartmannová, H.; Zaki, M.S.; Chaudhary, A.; Zudaire, E.; Nosková, L.; Barešová, V.; Přistoupilová, A.; Hodaňová, K.; Sovová, J.; Hůlková, H.; Piherová, L.; Hehir-Kwa, J.Y.; de Silva, D.; Senanayake, M.P.; Farrag, S.; Zeman, J.; Martásek, P.; Baxová, A.; Afifi, H.H.; St Croix, B.; Brunner, H.G.; Temtamy, S.; Kmoch, S.
    The genetic cause of GAPO syndrome, a condition characterized by growth retardation, alopecia, pseudoanodontia, and progressive visual impairment, has not previously been identified. We studied four ethnically unrelated affected individuals and identified homozygous nonsensemutations (c.262C>T [p.Arg88*] and c.505C>T [p.Arg169*]) or splicing mutations (c.1435-12A>G [p.Gly479Phefs*119]) in ANTXR1, which encodes anthrax toxin receptor 1. The nonsense mutations predictably trigger nonsense-mediated mRNA decay, resulting in the loss ofANTXR1. The transcript with the splicing mutation theoretically encodes a truncated ANTXR1 containing a neopeptide composed of 118 unique amino acids in its C terminus. GAPO syndrome's major phenotypic features, which include dental abnormalities and the accumulation of extracellular matrix, recapitulate those found in Antxr1-mutant mice and point toward an underlying defect in extracellular-matrix regulation. Thus, we propose that mutations affecting ANTXR1 function are responsible for this disease's characteristic generalized defect in extracellular-matrix homeostasis