Home
Resources
Publications
Human Osteoclast-Poor Osteopetrosis With Hypogammaglobulinemia Due to TNFRSF11A (RANK) Mutations

Human Osteoclast-Poor Osteopetrosis With Hypogammaglobulinemia Due to TNFRSF11A (RANK) Mutations

Matteo M Guerrini, Cristina Sobacchi, Barbara Cassani, Mario Abinun, Sara S Kilic, Alessandra Pangrazio, Daniele Moratto, Evelina Mazzolari, Jill Clayton-Smith, Paul Orchard, Fraser P Coxon, Miep H Helfrich, etc.

Am J Hum Genet. 2008 Jul;83(1):64-76.

PMID: 18606301

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413747	RANK Ligand/TRANCE human			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: