Osteoporosis, childhood- or juvenile-onset, with developmental delay (OPDD)
Description
Osteoporosis is a common disease characterised by a generalised reduction in bone mineral density (BMD), microarchitectural deterioration of bone tissue and an increased risk of fracture. Since BMD values fall progressively with age, the prevalence of osteoporosis increases with age. It has been estimated that approximately 50% of all women will have osteoporosis by the age of 80. Studies in twins and families indicate that genetic factors play an important role in the regulation of BMD and other determinants of osteoporotic fracture risk. Osteoporosis is a polygenic disorder, determined by the effects of several genes, each with relatively modest effects. Population-based studies and case-control studies have similarly identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, including the vitamin D receptor, oestrogen receptor and collagen gene. Bisphosphonates, and in some patients denosumab, are first-line drugs for osteoporosis.
Category
Musculoskeletal disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
15 Diseases of the musculoskeletal system or connective tissue
Osteopathies or chondropathies
FB83 Low bone mass disorders
H01593 Osteoporosis
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06505 WNT signaling
H01593 Osteoporosis
Cellular process
nt06539 Cytoskeleton in muscle cells
H01593 Osteoporosis
Omasu F, Ezura Y, Kajita M, Ishida R, Kodaira M, Yoshida H, Suzuki T, Hosoi T, Inoue S, Shiraki M, Orimo H, Emi M
Title
Association of genetic variation of the RIL gene, encoding a PDZ-LIM domain protein and localized in 5q31.1, with low bone mineral density in adult Japanese women.
Spotila LD, Constantinou CD, Sereda L, Ganguly A, Riggs BL, Prockop DJ
Title
Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta.
Yang TL, Chen XD, Guo Y, Lei SF, Wang JT, Zhou Q, Pan F, Chen Y, Zhang ZX, Dong SS, Xu XH, Yan H, Liu X, Qiu C, Zhu XZ, Chen T, Li M, Zhang H, Zhang L, Drees BM, Hamilton JJ, Papasian CJ, Recker RR, Song XP, Cheng J, Deng HW
Title
Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis.
Styrkarsdottir U, Thorleifsson G, Sulem P, Gudbjartsson DF, Sigurdsson A, Jonasdottir A, Jonasdottir A, Oddsson A, Helgason A, Magnusson OT, Walters GB, Frigge ML, Helgadottir HT, Johannsdottir H, Bergsteinsdottir K, Ogmundsdottir MH, Center JR, Nguyen TV, Eisman JA, Christiansen C, Steingrimsson E, Jonasson JG, Tryggvadottir L, Eyjolfsson GI, Theodors A, Jonsson T, Ingvarsson T, Olafsson I, Rafnar T, Kong A, Sigurdsson G, Masson G, Thorsteinsdottir U, Stefansson K
Title
Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits.
Hyperostosis corticalis generalisata is characterized by progressive bone overgrowth, with narrowing of the neuroforamina in the skull causing cranial neuropathies. Autosomal recessive hyperostosis corticalis generalisata is also known as Van Buchem disease (VBCH). VBCH is due to a homozygous deletion of a 52-kb regulatory element 35 kb downstream of the SOST gene, which leads to impaired production of sclerostin. Sclerostin, the gene product of SOST, is an inhibitor of the canonical Wnt signaling pathway. Hyperostosis corticalis generalisata can be caused by a mutation in the LRP5 gene.
Category
Musculoskeletal disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
15 Diseases of the musculoskeletal system or connective tissue
Osteopathies or chondropathies
FB80 Certain specified disorders of bone density or structure
H01774 Hyperostosis corticalis generalisata
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06505 WNT signaling
H01774 Hyperostosis corticalis generalisata
van Egmond ME, Dikkers FG, Boot AM, van Lierop AH, Papapoulos SE, Brouwer OF
Title
A rare cause of facial nerve palsy in children: hyperostosis corticalis generalisata (Van Buchem disease). Three new pediatric cases and a literature review.
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.
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 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-based classification of diseases [BR:br08402]
Signal transduction
nt06505 WNT signaling
H00436 Osteopetrosis
nt06516 TNF signaling
H00436 Osteopetrosis
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.
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.
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.
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.
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.
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.
Osteoporosis-pseudoglioma syndrome (OPPG) is inherited as an autosomal recessive condition and is characterized by severe congenital osteoporosis with blindness. Mutations in LRP5 cause OPPG.
Category
Congenital malformation
Brite
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
H00451 Osteoporosis-pseudoglioma syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06505 WNT signaling
H00451 Osteoporosis-pseudoglioma syndrome
Familial exudative vitreoretinopathy (FEVR) is inherited retinal disorders with ocular manifestations that are caused by alterations in the Wnt signaling network. FEVR has an abnormal vascularization of the peripheral retina with the formation of retinal folds, retinal detachment, and in many cases the creation of a fibrovascular membrane located behind the lens. Mutations in NDP, FZD4, and LRP5 have been reported to be responsible for ophthalmic diseases including Norrie disease, FEVR, and osteoporosis pseudoglioma syndrome. The proteins encoded by these genes have all been shown to participate in the Wnt/Norrin signaling pathway. Recently, heterozygous mutations in TSPAN12, which is a component of the Norrin-FZD4-LRP5 signaling complex, have been found to be responsible for autosomal dominant FEVR.
Category
Nervous system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Structural developmental anomalies primarily affecting one body system
Structural developmental anomalies of the eye, eyelid or lacrimal apparatus
LA13 Structural developmental anomalies of the posterior segment of eye
H00589 Familial exudative vitreoretinopathy
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06505 WNT signaling
H00589 Familial exudative vitreoretinopathy
Nikopoulos K, Venselaar H, Collin RW, Riveiro-Alvarez R, Boonstra FN, Hooymans JM, Mukhopadhyay A, Shears D, van Bers M, de Wijs IJ, van Essen AJ, Sijmons RH, Tilanus MA, van Nouhuys CE, Ayuso C, Hoefsloot LH, Cremers FP
Title
Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP.
