Skeletal dysplasias with increased bone density: evolution of molecular pathogenesis in the last century

Gene. 2013 Oct 1;528(1):41-5. doi: 10.1016/j.gene.2013.04.069. Epub 2013 May 5.


Skeletal dysplasias (SKD) with increased bone density form a discrete group of SKDs as per the Nosology and Classification of Genetic Skeletal Disorders, 2010 Revision. This group, with the prototype disorder being osteopetrosis, has evolved over the last century, with new entities being described & their molecular basis being increasingly elucidated. Osteopetrosis, which remained an enigma in the early part of its description, is now known to be genetically heterogenous. Other disorders in this group, which were initially described as variant forms of osteopetrosis, are now recognised to be distinct conditions. However, all these SKDs with increased bone density share their molecular pathogenesis as majority arise due to mutations in the genes governing osteoclast formation and function.

Keywords: AD; ANKH; AR; Autosomal dominant; Autosomal recessive; CA2; CLCN7; FERMT3; Genetics; History; Increased bone density; LEM domain containing 3 [Homo sapiens]; LEMD3; LRP5; NEMO; NF-kappa-B essential modulator [Homo sapiens]; OSTM1; Osteopetrosis; PLEKHM1; RANK; RANKL; SKD; SLC29A3; SNX10; SOST; Skeletal dysplasia; T-cell, immune regulator 1, ATPase, H(+) transporting, lysosomal V0 subunit A3 [Homo sapiens]; TCIRG1; TGFB1; WTX; Wilms tumor gene on the X chromosome protein [Homo sapiens]; ankylosis, progressive homolog (mouse) [Homo sapiens]; carbonic anhydrase II [Homo sapiens]; chloride channel, voltage-sensitive 7 [Homo sapiens]; fermitin family member 3 [Homo sapiens]; low density lipoprotein receptor-related protein 5 [Homo sapiens]; osteopetrosis associated transmembrane protein 1 [Homo sapiens]; pleckstrin homology domain containing, family M (with RUN domain) member 1 [Homo sapiens]; receptor activator of NF-KB [Homo Sapiens]; receptor activator of nuclear factor kappa B ligand [Homo Sapiens]; sclerostin [Homo sapiens]; solute carrier family 29 (nucleoside transporters), member 3 [Homo sapiens]; sorting nexin 10 [Homo sapiens]; transforming growth factor, beta 1 [Homo sapiens].

Publication types

  • Review

MeSH terms

  • Bone Density / genetics*
  • Evolution, Molecular
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Mutation
  • Osteopetrosis / genetics*
  • Osteopetrosis / pathology*
  • Phenotype
  • Vacuolar Proton-Translocating ATPases / genetics


  • TCIRG1 protein, human
  • Vacuolar Proton-Translocating ATPases