Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL.
Autosomal recessive osteopetrosis is usually associated with normal or elevated numbers of nonfunctional osteoclasts. Here we report mutations in the gene encoding RANKL (receptor activator of nuclear factor-KB ligand) in six individuals with autosomal recessive osteopetrosis whose bone biopsy specimens lacked osteoclasts. These individuals did not show any obvious defects in immunological parameters and could not be cured by hematopoietic stem cell transplantation; however, exogenous RANKL induced formation of functional osteoclasts from their monocytes, suggesting that they could, theoretically, benefit from exogenous RANKL administration.
Sobacchi
Cristina
C
Institute of Biomedical Technologies, Consiglio Nazionale delle Ricerche, via F. Cervi 93, 20090 Segrate, Italy.
Frattini
Annalisa
A
Guerrini
Matteo M
MM
Abinun
Mario
M
Pangrazio
Alessandra
A
Susani
Lucia
L
Bredius
Robbert
R
Mancini
Grazia
G
Cant
Andrew
A
Bishop
Nick
N
Grabowski
Peter
P
Del Fattore
Andrea
A
Messina
Chiara
C
Errigo
Gabriella
G
Coxon
Fraser P
FP
Scott
Debbie I
DI
Teti
Anna
A
Rogers
Michael J
MJ
Vezzoni
Paolo
P
Villa
Anna
A
Helfrich
Miep H
MH
D000818:Animals; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D051379:Mice; D010010:Osteoclasts; D010022:Osteopetrosis / Q000235:genetics*; D010375:Pedigree; D053245:RANK Ligand / Q000235:genetics*
D053245:RANK Ligand; C505688:TNFSF11 protein, human