Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse.
Nat Genet
; 20(2): 157-62, 1998 Oct.
Article
em En
| MEDLINE
| ID: mdl-9771708
ABSTRACT
The osteochondrodysplasias are a genetically heterogeneous group of disorders affecting skeletal development, linear growth and the maintenance of cartilage and bone. We have studied a large inbred Pakistani family with a distinct form of recessively inherited spondyloepimetaphyseal dysplasia (SEMD) and mapped a gene associated with this dwarfing condition to chromosome 10q23-24, a region syntenic with the locus for the brachymorphic mutation on mouse chromosome 19. We identified two orthologous genes, ATPSK2 and Atpsk2, encoding novel ATP sulfurylase/APS kinase orthologues in the respective regions of the human and mouse genomes. We characterized a nonsense mutation in ATPSK2 in the SEMD family and a missense mutation in the region of Atpsk2 encoding the APS kinase activity in the brachymorphic mouse. ATP sulfurylase/APS kinase catalyses the metabolic activation of inorganic sulfate to PAPS, the universal donor for post-translational protein sulfation in all cell types. The cartilage-specificity of the human and mouse phenotypes provides further evidence of the critical role of sulfate activation in the maturation of cartilage extracellular matrix molecules and the effect of defects in this process on the architecture of cartilage and skeletogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Osteocondrodisplasias
/
Cromossomos Humanos Par 10
/
Fosfotransferases (Aceptor do Grupo Álcool)
/
Mutação
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos