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.2014-10-292014-10-292013American Journal of Human Genetics; 92(5): pp.792-90002-9297 (Print)1537-6605 (Electronic)http://repository.kln.ac.lk/handle/123456789/2291The 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 homeostasisArticlePhysiology