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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-7-8
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-10500098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-10615125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-10888887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-10984520,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-11085748,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-11207362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-11242109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-11771666,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-12452182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-12627228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-12929927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-15231021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-15485878,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-15625335,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-16234979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-16373338,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-17098490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-17308995,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-17404618,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-17502664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-17632511,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18606301-9950424
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acid Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD45,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Osteoprotegerin,
http://linkedlifedata.com/resource/pubmed/chemical/RANK Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Activator of Nuclear...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vitronectin,
http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF11A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/tartrate-resistant acid phosphatase
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1537-6605
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pubmed:author |
pubmed-author:AbinunMarioM,
pubmed-author:CassaniBarbaraB,
pubmed-author:Clayton-SmithJillJ,
pubmed-author:CoxonFraser PFP,
pubmed-author:CrockettJulie CJC,
pubmed-author:FrattiniAnnalisaA,
pubmed-author:GuerriniMatteo MMM,
pubmed-author:HelfrichMiep HMH,
pubmed-author:KilicSara SSS,
pubmed-author:MazzolariEvelinaE,
pubmed-author:MellisDavidD,
pubmed-author:MorattoDanieleD,
pubmed-author:NotarangeloLuigi DLD,
pubmed-author:OrchardPaulP,
pubmed-author:PangrazioAlessandraA,
pubmed-author:RogersMichael JMJ,
pubmed-author:SobacchiCristinaC,
pubmed-author:TezcanIlhanI,
pubmed-author:VellodiAshokA,
pubmed-author:VezzoniPaoloP,
pubmed-author:VillaAnnaA
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pubmed:issnType |
Electronic
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pubmed:volume |
83
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
64-76
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pubmed:dateRevised |
2010-9-22
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pubmed:meshHeading |
pubmed-meshheading:18606301-Humans,
pubmed-meshheading:18606301-Biopsy,
pubmed-meshheading:18606301-Arginine,
pubmed-meshheading:18606301-Osteopetrosis,
pubmed-meshheading:18606301-Ilium,
pubmed-meshheading:18606301-Cysteine,
pubmed-meshheading:18606301-Lipopolysaccharides,
pubmed-meshheading:18606301-Acid Phosphatase,
pubmed-meshheading:18606301-Actins,
pubmed-meshheading:18606301-Female,
pubmed-meshheading:18606301-Male,
pubmed-meshheading:18606301-Osteoclasts,
pubmed-meshheading:18606301-Radiography, Thoracic,
pubmed-meshheading:18606301-Genes, Recessive,
pubmed-meshheading:18606301-Argentina,
pubmed-meshheading:18606301-Agammaglobulinemia,
pubmed-meshheading:18606301-Consanguinity,
pubmed-meshheading:18606301-Cells, Cultured,
pubmed-meshheading:18606301-Pedigree
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