PMID- 10615125
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20061115
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 24
IP  - 1
DP  - 2000 Jan
TI  - Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial
      expansile osteolysis.
PG  - 45-8
AB  - Familial expansile osteolysis (FEO, MIM 174810) is a rare, autosomal dominant
      bone disorder characterized by focal areas of increased bone remodelling. The
      osteolytic lesions, which develop usually in the long bones during early
      adulthood, show increased osteoblast and osteoclast activity. Our previous
      linkage studies mapped the gene responsible for FEO to an interval of less than 5
      cM between D18S64 and D18S51 on chromosome 18q21.2-21.3 in a large Northern Irish
      family. The gene encoding receptor activator of nuclear factor-kappa B (RANK;
      ref. 5), TNFRSF11A, maps to this region. RANK is essential in osteoclast
      formation. We identified two heterozygous insertion mutations in exon 1 of
      TNFRSF11A in affected members of four families with FEO or familial Paget disease
      of bone (PDB). One was a duplication of 18 bases and the other a duplication of
      27 bases, both of which affected the signal peptide region of the RANK molecule. 
      Expression of recombinant forms of the mutant RANK proteins revealed
      perturbations in expression levels and lack of normal cleavage of the signal
      peptide. Both mutations caused an increase in RANK-mediated nuclear factor-kappaB
      (NF-kappaB) signalling in vitro, consistent with the presence of an activating
      mutation.
FAU - Hughes, A E
AU  - Hughes AE
AD  - Department of Medical Genetics, The Queen's University of Belfast, Belfast, UK.
      A.Hughes@qub.ac.uk
FAU - Ralston, S H
AU  - Ralston SH
FAU - Marken, J
AU  - Marken J
FAU - Bell, C
AU  - Bell C
FAU - MacPherson, H
AU  - MacPherson H
FAU - Wallace, R G
AU  - Wallace RG
FAU - van Hul, W
AU  - van Hul W
FAU - Whyte, M P
AU  - Whyte MP
FAU - Nakatsuka, K
AU  - Nakatsuka K
FAU - Hovy, L
AU  - Hovy L
FAU - Anderson, D M
AU  - Anderson DM
LA  - eng
SI  - GENBANK/AF018253
SI  - GENBANK/AF019046
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Protein Sorting Signals)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNFRSF11A protein, human)
RN  - 0 (TNFSF11 protein, human)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Base Sequence
MH  - *Carrier Proteins
MH  - DNA
MH  - Female
MH  - Humans
MH  - Male
MH  - *Membrane Glycoproteins
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Osteolysis/*genetics
MH  - Pedigree
MH  - Protein Sorting Signals/*genetics
MH  - RANK Ligand
MH  - Receptor Activator of Nuclear Factor-kappa B
MH  - Receptors, Tumor Necrosis Factor/*chemistry/*genetics
EDAT- 1999/12/30 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/12/30 09:00
PHST- 1999/12/30 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/12/30 09:00 [entrez]
AID - 10.1038/71667 [doi]
PST - ppublish
SO  - Nat Genet. 2000 Jan;24(1):45-8. doi: 10.1038/71667.