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Previous Volume 347:175-184 July 18, 2002 Number 3 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Krane, S. M. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Juvenile Paget's disease, an autosomal recessive osteopathy, is characterized by rapidly remodeling woven bone, osteopenia, fractures, and progressive skeletal deformity. The molecular basis is not known. Osteoprotegerin deficiency could explain juvenile Paget's disease because osteoprotegerin suppresses bone turnover by functioning as a decoy receptor for osteoclast differentiation factor (also called RANK ligand).

Methods We evaluated two apparently unrelated Navajo patients with juvenile Paget's disease for defects in the gene encoding osteoprotegerin (TNFRSF11B) using polymerase-chain-reaction (PCR) amplification followed by direct sequencing and Southern blotting of genomic DNA. Genetic markers near TNFRSF11B were evaluated by both a PCR method that involved sequence-tagged site-content mapping of a deletion of TNFRSF11B and PCR spanning the DNA break points.

Results Both patients had a homozygous deletion of TNFRSF11B, with identical break points, on chromosome 8q24.2. The defect spans approximately 100 kb, but neighboring genes are intact. We found that serum levels of osteoprotegerin and soluble osteoclast differentiation factor were undetectable and markedly increased, respectively.

Conclusions Juvenile Paget's disease can result from osteoprotegerin deficiency caused by homozygous deletion of TNFRSF11B.

Source Information

From the Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children (M.P. W., M.N.P., S.M.); the Division of Bone and Mineral Diseases, Washington University School of Medicine at Barnes–Jewish Hospital (M.P. W., S.E.O., P.M.F., J.L.J., S.M.); and Mallinckrodt Institute of Radiology, Washington University School of Medicine at St. Louis Children's Hospital (W.H.M.) — all in St. Louis.

Address reprint requests to Dr. Whyte at Shriners Hospitals for Children, 2001 S. Lindbergh Blvd., St. Louis, MO 63131, or at mwhyte{at}shrinenet.org.

Full Text of this Article

Related Letters:

Osteoprotegerin Deficiency and Juvenile Paget's Disease
Hofbauer L. C., Schoppet M., Whyte M. P., Podgornik M. N., Mumm S.
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N Engl J Med 2002; 347:1622-1623, Nov 14, 2002. Correspondence

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