Mutations in ANTXR1 cause GAPO syndrome.
Am J Hum Genet
; 92(5): 792-9, 2013 May 02.
Article
de En
| MEDLINE
| ID: mdl-23602711
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Chromosomes humains de la paire 2
/
Atrophies optiques héréditaires
/
Récepteurs de surface cellulaire
/
Prédisposition génétique à une maladie
/
Alopécie
/
Matrice extracellulaire
/
Troubles de la croissance
/
Homéostasie
/
Anodontie
/
Protéines tumorales
Type d'étude:
Prognostic_studies
Limites:
Humans
/
Male
Langue:
En
Journal:
Am J Hum Genet
Année:
2013
Type de document:
Article
Pays d'affiliation:
République tchèque