Osteopetrosis, Autosomal recessive 7 (OPTB7)

(OMIM phenotype number #612301)

Osteopetrosis, Autosomal recessive 7, is a form of osteoclast-poor autosomal recessive osteopetrosis (see OPTB1), and it can be caused by mutation in the tumor necrosis factor receptor superfamily, member 11a (TNFRSF11A) gene. As opposed to TNFSF11 deficiency, osteopetrosis in TNFRSF11A-deficient patients could be rescued by hematopoietic stem cell transplantation.

Gene

TNFRSF11A gene, 18q21.33 (OMIM gene/locus number #603499), encoding receptor activator of NF kappa B (RANK). RANKL, the protein coded for by the TNFSF11 gene, binds to RANK, a membrane-anchored receptor, and RANKL signaling through RANK is fundamental for osteoclast maturation.

Phenotype

Severe form, osteoclast-poor, increased bone density (sclerosis) and generalized high bone mass, hypogammaglobulinemia.

Main biochemical alterations:

Adult/intermediate forms: high CK-BB, high bone ALP. Infantile/severe forms: low Ca, high PTH, high 1,25(OH)2D, high CK-BB, high AP.

Images

b

Fig. Radiographies show: (a,b) Bone thickening of vertebrae and ribs is evident, revealing classical osteopetrotic phenotype.

Reproduced from Am J Hum Genet, Vol 83, Guerrini MM, Sobacchi C, Cassani B, et al. Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations, Pages 64-76, Copyright 2008, with permission from Elsevier.



Other resource : http://www.osteopetrosis.org/


References

  1. Guerrini MM, Sobacchi C, Cassani B, et al. Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. Am J Hum Genet. 2008 Jul;83(1):64-76. doi: 10.1016/j.ajhg.2008.06.015.
  2. De Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  3. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  4. http://www.omim.org