KEGG   DISEASE: Osteopetrosis
Entry
H00436                      Disease                                

Name
Osteopetrosis
  Subgroup
Osteopetrosis, autosomal dominant (OPTA)
Osteopetrosis, autosomal recessive (OPTB)
Description
The osteopetroses are a heterogeneous group of disorders characterized by increased bone density and the replacement of trabecular bone with compact bone due to reduced osteoclastic bone resorption. Some osteopetrotic conditions exhibit additional clinical features including renal tubular acidosis and secondary neurological impairment. In forms of osteopetrosis with normal osteoclast counts, most of the mutated genes encode proteins that regulate the intra- and extracellular pH of osteoclasts, such as TCIRG1 gene encoding for the a3 subunit of the V-ATPase and CLCN7 gene. In cases with decreased osteoclast counts, osteoclast differentiation is impaired by mutations in RANKL or RANK. These RANK-deficient patients could be rescued by hematopoietic stem cell transplantation.
Category
Congenital malformation
Brite
Human diseases [BR:br08402]
 Congenital malformations
  Congenital malformations of the musculoskeletal system
   H00436  Osteopetrosis
Human diseases in ICD-11 classification [BR:br08403]
 20 Developmental anomalies
  Multiple developmental anomalies or syndromes
   LD24  Syndromes with skeletal anomalies as a major feature
    H00436  Osteopetrosis
Pathway
hsa04380  Osteoclast differentiation
hsa05323  Rheumatoid arthritis
Gene
(OPTA1) LRP5 [HSA:4041] [KO:K03068]
(OPTA2/B4) CLCN7 [HSA:1186] [KO:K05016]
(OPTB1) TCIRG1 [HSA:10312] [KO:K02154]
(OPTB2) RANKL [HSA:8600] [KO:K05473]
(OPTB3) CA2 [HSA:760] [KO:K18245]
(OPTB5) OSTM1 [HSA:28962] [KO:K23863]
(OPTB6) PLEKHM1 [HSA:9842] [KO:K23282]
(OPTB7) RANK [HSA:8792] [KO:K05147]
(OPTB8) SNX10 [HSA:29887] [KO:K17924]
Drug
Interferon gamma-1b [DR:D00747]
Comment
OBTB1, OPTB4, OBTP5, and OBTP8 are infantile malignant osteopetrosis.
OPTB3 is osteopetrosis associated with renal tubular acidosis.
Other DBs
ICD-11: LD24.10
ICD-10: Q78.2
MeSH: D010022
OMIM: 607634 166600 259700 259710 259730 611490 259720 611497 612301 615085
Reference
  Authors
Michou L, Brown JP
  Title
Genetics of bone diseases: Paget's disease, fibrous dysplasia, osteopetrosis, and osteogenesis imperfecta.
  Journal
Joint Bone Spine 78:252-8 (2011)
DOI:10.1016/j.jbspin.2010.07.010
Reference
  Authors
Balemans W, Van Wesenbeeck L, Van Hul W
  Title
A clinical and molecular overview of the human osteopetroses.
  Journal
Calcif Tissue Int 77:263-74 (2005)
DOI:10.1007/s00223-005-0027-6
Reference
  Authors
Del Fattore A, Cappariello A, Teti A
  Title
Genetics, pathogenesis and complications of osteopetrosis.
  Journal
Bone 42:19-29 (2008)
DOI:10.1016/j.bone.2007.08.029
Reference
  Authors
Schulz A, Kornak U
  Title
CLCN7-Related Osteopetrosis
  Journal
GeneReviews (1993)
Reference
  Authors
Del Fattore A, Fornari R, Van Wesenbeeck L, de Freitas F, Timmermans JP, Peruzzi B, Cappariello A, Rucci N, Spera G, Helfrich MH, Van Hul W, Migliaccio S, Teti A
  Title
A new heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin homolog domain containing family M (with run domain) member 1 (PLEKHM1), impairs vesicular acidification and increases TRACP secretion in osteoclasts.
  Journal
J Bone Miner Res 23:380-91 (2008)
DOI:10.1359/jbmr.071107
Reference
  Authors
Sobacchi C, Frattini A, Guerrini MM, Abinun M, Pangrazio A, Susani L, Bredius R, Mancini G, Cant A, Bishop N, Grabowski P, Del Fattore A, Messina C, Errigo G, Coxon FP, Scott DI, Teti A, Rogers MJ, Vezzoni P, Villa A, Helfrich MH
  Title
Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL.
  Journal
Nat Genet 39:960-2 (2007)
DOI:10.1038/ng2076
Reference
  Authors
Guerrini MM, Sobacchi C, Cassani B, Abinun M, Kilic SS, Pangrazio A, Moratto D, Mazzolari E, Clayton-Smith J, Orchard P, Coxon FP, Helfrich MH, Crockett JC, Mellis D, Vellodi A, Tezcan I, Notarangelo LD, Rogers MJ, Vezzoni P, Villa A, Frattini A
  Title
Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations.
  Journal
Am J Hum Genet 83:64-76 (2008)
DOI:10.1016/j.ajhg.2008.06.015
Reference
PMID:6702897
  Authors
Kahler SG, Burns JA, Aylsworth AS
  Title
A mild autosomal recessive form of osteopetrosis.
  Journal
Am J Med Genet 17:451-64 (1984)
DOI:10.1002/ajmg.1320170208
Reference
  Authors
Aker M, Rouvinski A, Hashavia S, Ta-Shma A, Shaag A, Zenvirt S, Israel S, Weintraub M, Taraboulos A, Bar-Shavit Z, Elpeleg O
  Title
An SNX10 mutation causes malignant osteopetrosis of infancy.
  Journal
J Med Genet 49:221-6 (2012)
DOI:10.1136/jmedgenet-2011-100520

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