Brief Communication abstract
Nature Genetics 39, 960 - 962 (2007)
Published online: 15 July 2007 | doi:10.1038/ng2076
Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL
Cristina Sobacchi1,2, Annalisa Frattini1, Matteo M Guerrini1,2, Mario Abinun3, Alessandra Pangrazio1, Lucia Susani1, Robbert Bredius4, Grazia Mancini5, Andrew Cant3, Nick Bishop6, Peter Grabowski6, Andrea Del Fattore7, Chiara Messina8, Gabriella Errigo8, Fraser P Coxon9, Debbie I Scott9, Anna Teti7, Michael J Rogers9, Paolo Vezzoni1, Anna Villa1,10 & Miep H Helfrich9
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.
- Institute of Biomedical Technologies, Consiglio Nazionale delle Ricerche, via F. Cervi 93, 20090 Segrate, Italy.
- Istituto Clinico Humanitas, 20089 Rozzano, Italy.
- Children's Bone Marrow Transplant Unit, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK, and Institute for Cellular Medicine, Faculty of Medicine, Newcastle upon Tyne NE4 6BE, UK.
- Department of Pediatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
- Department of Clinical Genetics, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
- Academic Unit of Child Health, University of Sheffield, Sheffield S10 2TH, UK.
- Department of Experimental Medicine, University of L'Aquila, 67100 L'Aquila, Italy.
- Pediatric Hematology and Oncology Unit, University of Padova, 35122 Padova, Italy.
- Bone & Musculoskeletal Programme, University of Aberdeen, Aberdeen AB25 2ZD, UK.
- Università Vita e Salute San Raffaele, Telethon Institute for Gene Therapy, 20090 Milan, Italy.
Correspondence to: Annalisa Frattini1 e-mail: annalisa.frattini@itb.cnr.it
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