title: Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL.
abstract: 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.
authors.affiliation: Institute of Biomedical Technologies, Consiglio Nazionale delle Ricerche, via F. Cervi 93, 20090 Segrate, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sobacchi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Frattini
authors.forename: Matteo M
authors.initials: MM
authors.lastname: Guerrini
authors.forename: Mario
authors.initials: M
authors.lastname: Abinun
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pangrazio
authors.forename: Lucia
authors.initials: L
authors.lastname: Susani
authors.forename: Robbert
authors.initials: R
authors.lastname: Bredius
authors.forename: Grazia
authors.initials: G
authors.lastname: Mancini
authors.forename: Andrew
authors.initials: A
authors.lastname: Cant
authors.forename: Nick
authors.initials: N
authors.lastname: Bishop
authors.forename: Peter
authors.initials: P
authors.lastname: Grabowski
authors.forename: Andrea
authors.initials: A
authors.lastname: Del Fattore
authors.forename: Chiara
authors.initials: C
authors.lastname: Messina
authors.forename: Gabriella
authors.initials: G
authors.lastname: Errigo
authors.forename: Fraser P
authors.initials: FP
authors.lastname: Coxon
authors.forename: Debbie I
authors.initials: DI
authors.lastname: Scott
authors.forename: Anna
authors.initials: A
authors.lastname: Teti
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rogers
authors.forename: Paolo
authors.initials: P
authors.lastname: Vezzoni
authors.forename: Anna
authors.initials: A
authors.lastname: Villa
authors.forename: Miep H
authors.initials: MH
authors.lastname: Helfrich
mesh_terms: 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*
chemical_list: D053245:RANK Ligand; C505688:TNFSF11 protein, human