Osteopetrosis, Autosomal recessive 8 (OPTB8)

(OMIM phenotype number #615085)

Osteopetrosis, Autosomal recessive 8, is a form of osteoclast-poor autosomal recessive osteopetrosis (see OPTB1), and it is caused by homozygous mutation in the sorting nexin 10 (SNX10) gene. This gene has been shown to be involved in the process of osteoclast differentiation and function upon RANKL-stimulation.

Gene

SNX10 gene, 7p15.2 (OMIM gene/locus number #614780). SNX10 has been recently shown to interact with vacuolar type H(+)-ATPase (V-ATPase) which pumps protons at the osteoclast-bone interface. A mutation in SNX10 may therefore result in 'secondary V-ATPase deficiency' with a failure to acidify the resorption lacuna.

Phenotype

Severe form, loss of trabecular structure, poor/no definition between cortical and medullary bone, macrocephaly, failure to thrive, macrocephaly, frontal bossing, facial nerve palsy, optic nerve atrophy, nasal stuffiness due to fully ossified sinuses, narrowed medullary space due to encroachment of cortical bone, narrowed auditory canal, sclerosis of semicircular canals, narrow optic canal, narrow auditory canal, sclerosis of semicircular canals, fully ossified ethmoid air cells, fully ossified sphenoid sinuses, anemia, thrombocytopenia, bone marrow insufficiency, hepatosplenomegaly.

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, anemia.

Other resource

Osteopetrosis Society (OPETS)

References

  1. Aker M, Rouvinski A, Hashavia S, et al. An SNX10 mutation causes malignant osteopetrosis of infancy. J Med Genet. 2012 Apr;49(4):221-6.
  2. Pangrazio A, Fasth A, Sbardellati A, et al. SNX10 mutations define a subgroup of human autosomal recessive osteopetrosis with variable clinical severity. J Bone Miner Res. 2013 May;28(5):1041-9. doi: 10.1002/jbmr.1849.
  3. De Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  4. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  5. http://www.omim.org