Mutations in ANTXR1 cause GAPO syndrome

Viktor Stránecký, Alexander Hoischen, Hana Hartmannová, Maha S. Zaki, Amit Chaudhary, Enrique Zudaire, Lenka Nosková, Veronika Barešová, Anna Přistoupilová, Kateřina Hodaňová, Jana Sovová, Helena Hůlková, Lenka Piherová, Jayne Y. Hehir-Kwa, Deepthi De Silva, Manouri P. Senanayake, Sameh Farrag, Jiří Zeman, Pavel Martásek, Alice BaxováHanan H. Afifi, Brad St. Croix, Han G. Brunner, Samia Temtamy, Stanislav Kmoch

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

66 Citaten (Scopus)

Samenvatting

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 nonsense mutations (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 of ANTXR1. 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.

Originele taal-2Engels
Pagina's (van-tot)792-799
Aantal pagina's8
TijdschriftAmerican Journal of Human Genetics
Volume92
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 2 mei 2013
Extern gepubliceerdJa

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