| H00436 | |
| H number | H00436 |
| Name | Osteopetrosis |
| 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 |
| Network | - |
| Gene | (OPTA1) LRP5 [HSA:4041] [KO:K03068] (OPTA2/B4) CLCN7 [HSA:1186] [KO:K05016] (OPTA3/B6) PLEKHM1 [HSA:9842] [KO:K23282] (OPTB1) TCIRG1 [HSA:10312] [KO:K02154] (OPTB2) TNFSF11 [HSA:8600] [KO:K05473] (OPTB3) CA2 [HSA:760] [KO:K18245] (OPTB5) OSTM1 [HSA:28962] [KO:K23863] (OPTB7) TNFRSF11A [HSA:8792] [KO:K05147] (OPTB8) SNX10 [HSA:29887] [KO:K17924] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| 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 618107 259700 259710 259730 611490 259720 611497 612301 615085 |
| Reference | PMID:20855225 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 PMID:16307387 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 PMID:17936098 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 PMID:12579474 (LRP5) AUTHORS Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Benichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, De Vernejoul MC, Bollerslev J, Van Hul W TITLE Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. JOURNAL Am J Hum Genet 72:763-71 (2003) DOI:10.1086/368277 PMID:11741829 (CLCN7, OPTA2) AUTHORS Cleiren E, Benichou O, Van Hul E, Gram J, Bollerslev J, Singer FR, Beaverson K, Aledo A, Whyte MP, Yoneyama T, deVernejoul MC, Van Hul W TITLE Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. JOURNAL Hum Mol Genet 10:2861-7 (2001) DOI:10.1093/hmg/10.25.2861 PMID:17997709 (PLEKHM1, OPTA3) 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 PMID:10888887 (TCIRG1) AUTHORS Frattini A, Orchard PJ, Sobacchi C, Giliani S, Abinun M, Mattsson JP, Keeling DJ, Andersson AK, Wallbrandt P, Zecca L, Notarangelo LD, Vezzoni P, Villa A TITLE Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. JOURNAL Nat Genet 25:343-6 (2000) DOI:10.1038/77131 PMID:17632511 (TNFSF11) 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 PMID:1928091 (CA2) AUTHORS Venta PJ, Welty RJ, Johnson TM, Sly WS, Tashian RE TITLE Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene. JOURNAL Am J Hum Genet 49:1082-90 (1991) PMID:11207362 (CLCN7, OPTB4) AUTHORS Kornak U, Kasper D, Bosl MR, Kaiser E, Schweizer M, Schulz A, Friedrich W, Delling G, Jentsch TJ TITLE Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. JOURNAL Cell 104:205-15 (2001) DOI:10.1016/s0092-8674(01)00206-9 PMID:12627228 (OSTM1) AUTHORS Chalhoub N, Benachenhou N, Rajapurohitam V, Pata M, Ferron M, Frattini A, Villa A, Vacher J TITLE Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human. JOURNAL Nat Med 9:399-406 (2003) DOI:10.1038/nm842 PMID:17404618 (PLEKHM1, OPTB6) AUTHORS Van Wesenbeeck L, Odgren PR, Coxon FP, Frattini A, Moens P, Perdu B, MacKay CA, Van Hul E, Timmermans JP, Vanhoenacker F, Jacobs R, Peruzzi B, Teti A, Helfrich MH, Rogers MJ, Villa A, Van Hul W TITLE Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. JOURNAL J Clin Invest 117:919-30 (2007) DOI:10.1172/JCI30328 PMID:18606301 (TNFRSF11A) 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 PMID:22499339 (SNX10) 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 |