A Clinical and Molecular Overview of the Human Osteopetroses

Balemans, Wendy; Wesenbeeck, Liesbeth Van; Hul, Wim Van

doi:10.1007/s00223-005-0027-6

Cited by 134 publications

(124 citation statements)

References 79 publications

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“…2 At least three gene mutations have been identified accounting for approximately 70% of cases. 3 The changes seen in our patient are typical of the early appearance of IARMO. With time there is progressive metaphyseal widening producing an Erlenmeyer flask deformity and increased calvarial sclerosis.…”

Section: Denouement and Discussionsupporting

confidence: 63%

Infantile autosomal-recessive malignant osteopetrosis

Herman

Siegel

2007

J Perinatol

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Section: Denouement and Discussionsupporting

confidence: 63%

Infantile autosomal-recessive malignant osteopetrosis

Herman

Siegel

2007

J Perinatol

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“…It is important to note, however, that severe osteoporosis and fragility fractures or unusually high bone mass (HBM) can also be an important feature of rare diseases that are primarily genetic in nature and are inherited in a classical Mendelian manner. Such diseases include osteopetrosis, sclerosing bone dysplasias, osteogenesis imperfecta, osteoporosis-pseudoglioma syndrome (OPPS), and osteoporotic syndromes associated with inactivating mutations of the estrogen receptor ␣ and aromatase genes (Bilezikian et al 1998;Janssens and Van Hul 2002;Van Wesenbeeck et al 2003;Balemans et al 2005). Although these diseases are rare, increasing evidence suggests that subtle polymorphic variations in genes that are mutated in these disorders also regulate BMD in the general population.…”

Section: Genetic Influences On Osteoporosismentioning

confidence: 99%

“…Linkage studies have been spectacularly successful in identifying the genes that are responsible for rare, monogenic bone diseases characterized by abnormalities of bone mass such as osteopetrosis and sclerosing bone dysplasias (Janssens and Van Hul 2002;Balemans et al 2005). Linkage analysis has also been applied to the identification of chromosomal regions that harbor genes that regulate quantitative traits such as bone mass, bone geometry, and ultrasound properties of bone in the normal population (Koller et al 2003;Wilson et al 2003Wilson et al , 2004Ralston 2005).…”

Section: Linkage Analysis In Humansmentioning

confidence: 99%

“…Both are characterized by progressive osteosclerosis mainly affecting the skull, mandible, and tubular bones of the extremities (Beighton et al 1984). Sclerosteosis differs from van Buchem disease because it is more severe and is associated with hand malformations such as syndactyly, absent or dysplastic nails, and radial deviation of the terminal phalanges (Balemans et al 2005). Both diseases were mapped to the same region of chromosome 17q12-21 in the late 1990s (Van Hul et al 1998;Balemans et al 1999), and positional cloning studies identified recessive loss-of-function mutations in Sclerostin (SOST) gene as the cause of Sclerosteosis in 2001 (Balemans et al 2001;Brunkow et al 2001).…”

Section: Sclerostinmentioning

confidence: 99%

“…Homozygous inactivation mutations in CLCN7 cause a severe form of recessive osteopetrosis (Kornak et al 2001), whereas heterozygous missense mutations of CLCN7 cause autosomal dominant osteopetrosis (Balemans et al 2005). Prompted by this observation, Pettersson et al (2005) looked for evidence of an association between polymorphisms of CLCN7 and BMD in normal individuals and found that a common polymorphism in exon 15 of CLCN7 that results in a methionine-to-valine amino acid change was associated with BMD in normal women.…”

Section: Clcn7mentioning

confidence: 99%

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Genetic regulation of bone mass and susceptibility to osteoporosis

Ralston¹,

Crombrugghe²

2006

Genes Dev.

290

228

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Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and increased risk of fragility fractures. Twin and family studies have shown that the heritability of bone mineral density (BMD) and other determinants of fracture risksuch as ultrasound properties of bone, skeletal geometry, and bone turnover-is high, although heritability of fracture is modest. Many different genetic variants of modest effect size are likely to contribute to the regulation of these phenotypes by interacting with environmental factors such as diet and exercise. Linkage studies in rare Mendelian bone diseases have identified several previously unknown genes that play key roles in regulating bone mass and bone turnover. In many instances, subtle polymorphisms in these genes have also been found to regulate BMD in the general population. Although there has been extensive progress in identifying the genetic variants that regulate susceptibility to osteoporosis, most of the genes and genetic variants that regulate bone mass and susceptibility to osteoporosis remain to be discovered.Osteoporosis is characterized by reduced bone mass, alterations in the microarchitecture of bone tissue, reduced bone strength, and an increased risk of fracture (Kanis et al. 1994). Osteoporosis is a common condition that affects up to 30% of women and 12% of men at some point in life. The prevalence of osteoporosis increases with age due to an imbalance in the rate at which bone is removed and replaced during the bone remodeling cycle, which is an important physiological process that is essential for maintenance of a healthy skeleton. Many factors influence the risk of osteoporosis-including diet, physical activity, medication use, and coexisting diseases-but one of the most important clinical risk factors is a positive family history, emphasizing the importance of genetics in the pathogenesis of osteoporosis. In this article, we first review the evidence for a genetic contribution to osteoporosis and related phenotypes, and discuss the mechanisms by which mutations and polymorphisms in genes that regulate susceptibility to osteoporosis affect major signaling pathways in bone. Genetic influences on osteoporosisGenetic factors have long been recognized as playing an important role in the pathogenesis of osteoporosis. Evidence from twin and family studies suggests that between 50% and 85% of the variance in peak bone mass is genetically determined, depending on skeletal site and the age of the subjects studied (Smith et al. 1973;Pocock et al. 1987;Krall and Dawson-Hughes 1993;Gueguen et al. 1995). Heritability studies have also shown evidence of significant genetic effects on other key determinants of osteoporotic fracture risk, including quantitative ultrasound properties of bone (Arden et al. 1996), femoral neck geometry (Arden et al. 1996), muscle strength (Arden and Spector 1997), bone turnover markers (Hunter et al. 2001), and body mass index (Kaprio et al. 1995). The role of genetic factors in the pathogenesis of bon...

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Osteoporosis and Osteopetrosis

Abu‐Amer

Darwech

Otero

2007

Encyclopedia of Life Sciences

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Osteoporosis is the most prevalent among bone diseases. It is manifested by low bone mass and architectural abnormalities that lead to bone fragility and elevated fracture risk. Mechanistically, osteoporosis occurs as a result of decreased bone formation (by osteoblasts) and increased bone resorption (by osteoclasts). Thus, a tip in the balance favouring bone resorption results in osteoporosis e.g. porous bone. A wide range of factors contribute to the development of osteoporosis including genetic predisposition, ageing, reduced physical activity, diet, hormonal changes and more. Osteopetrosis, however, reflects the state of dense yet fragile bones due to dysfunctional or lack of osteoclasts.

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A Clinical and Molecular Overview of the Human Osteopetroses

Cited by 134 publications

References 79 publications

Infantile autosomal-recessive malignant osteopetrosis

Infantile autosomal-recessive malignant osteopetrosis

Genetic regulation of bone mass and susceptibility to osteoporosis

Osteoporosis and Osteopetrosis

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