Mutations in ANTXR1 cause GAPO syndrome.

Authors: Stranecky, V  Hoischen, A  Hartmannova, H  Zaki, MS  Chaudhary, A  Zudaire, E  Noskova, L  Baresova, V  Pristoupilova, A  Hodanova, K  Sovova, J  Hulkova, H  Piherova, L  Hehir-Kwa, JY  De Silva, D  Senanayake, MP  Farrag, S  Zeman, J  Martasek, P  Baxova, A  Afifi, HH  St Croix, B  Brunner, HG  Temtamy, S  Kmoch, S 
Citation: Stranecky V, etal., Am J Hum Genet. 2013 May 2;92(5):792-9. doi: 10.1016/j.ajhg.2013.03.023. Epub 2013 Apr 18.
Pubmed: (View Article at PubMed) PMID:23602711
DOI: Full-text: DOI:10.1016/j.ajhg.2013.03.023

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.


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CRRD Object Information
CRRD ID: 9684854
Created: 2014-12-09
Species: All species
Last Modified: 2014-12-09
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.