Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice.
Nat Genet
; 45(9): 1077-82, 2013 Sep.
Article
in En
| MEDLINE
| ID: mdl-23913003
ABSTRACT
Calcifications in the basal ganglia are a common incidental finding and are sometimes inherited as an autosomal dominant trait (idiopathic basal ganglia calcification (IBGC)). Recently, mutations in the PDGFRB gene coding for the platelet-derived growth factor receptor ß (PDGF-Rß) were linked to IBGC. Here we identify six families of different ancestry with nonsense and missense mutations in the gene encoding PDGF-B, the main ligand for PDGF-Rß. We also show that mice carrying hypomorphic Pdgfb alleles develop brain calcifications that show age-related expansion. The occurrence of these calcium depositions depends on the loss of endothelial PDGF-B and correlates with the degree of pericyte and blood-brain barrier deficiency. Thus, our data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Basal Ganglia Diseases
/
Calcinosis
/
Proto-Oncogene Proteins c-sis
/
Mutation
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2013
Document type:
Article
Affiliation country:
Suiza