| http://purl.uniprot.org/citations/18606301 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18606301 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18606301 | http://www.w3.org/2000/01/rdf-schema#comment | "Autosomal-Recessive Osteopetrosis (ARO) comprises a heterogeneous group of bone diseases for which mutations in five genes are known as causative. Most ARO are classified as osteoclast-rich, but recently a subset of osteoclast-poor ARO has been recognized as due to a defect in TNFSF11 (also called RANKL or TRANCE, coding for the RANKL protein), a master gene driving osteoclast differentiation along the RANKL-RANK axis. RANKL and RANK (coded for by the TNFRSF11A gene) also play a role in the immune system, which raises the possibility that defects in this pathway might cause osteopetrosis with immunodeficiency. From a large series of ARO patients we selected a Turkish consanguineous family with two siblings affected by ARO and hypogammaglobulinemia with no defects in known osteopetrosis genes. Sequencing of genes involved in the RANKL downstream pathway identified a homozygous mutation in the TNFRSF11A gene in both siblings. Their monocytes failed to differentiate in vitro into osteoclasts upon exposure to M-CSF and RANKL, in keeping with an osteoclast-intrinsic defect. Immunological analysis showed that their hypogammaglobulinemia was associated with impairment in immunoglobulin-secreting B cells. Investigation of other patients revealed a defect in both TNFRSF11A alleles in six additional, unrelated families. Our results indicate that TNFRSF11A mutations can cause a clinical condition in which severe ARO is associated with an immunoglobulin-production defect."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2008.06.015"xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2008.06.015"xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Villa A."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Villa A."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Abinun M."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Abinun M."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Notarangelo L.D."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Notarangelo L.D."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Tezcan I."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Tezcan I."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Clayton-Smith J."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Clayton-Smith J."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Vellodi A."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Vellodi A."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Frattini A."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Frattini A."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Vezzoni P."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Vezzoni P."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Moratto D."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Moratto D."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Kilic S.S."xsd:string |
| http://purl.uniprot.org/citations/18606301 | http://purl.uniprot.org/core/author | "Kilic S.S."xsd:string |