Sclerosing bone dysplasias

Boudin, Eveline; Hul, Wim Van

doi:10.1016/j.beem.2018.06.003

Cited by 20 publications

(7 citation statements)

References 139 publications

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“…Fractures secondary to bone brittleness are a classical feature of osteopetrotic syndromes, rather than to elevated BMD values due to supraphysiological bone formation, which is typically associated to decreased fracture risk. (65) Additionally, the presence of these two variants in the proband and only one of them in the mother and in the daughter with high BMD could explain the higher BMD found in the proband.…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis in a Familial Case With High Bone Mineral Density Suggests Additive Effects at Two Loci

et al. 2022

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Osteoporosis is the most common bone disease, characterized by a low bone mineral density (BMD) and increased risk of fracture. At the other end of the BMD spectrum, some individuals present strong, fracture‐resistant, bones. Both osteoporosis and high BMD are heritable and their genetic architecture encompasses polygenic inheritance of common variants and some cases of monogenic highly penetrant variants in causal genes. We have investigated the genetics of high BMD in a family segregating this trait in an apparently Mendelian dominant pattern. We searched for rare causal variants by whole‐exome sequencing in three affected and three nonaffected family members. Using this approach, we have identified 38 rare coding variants present in the proband and absent in the three individuals with normal BMD. Although we have found four variants shared by the three affected members of the family, we have not been able to relate any of these to the high‐BMD phenotype. In contrast, we have identified missense variants in two genes, VAV3 and ADGRE5, each shared by two of out of three affected members, whose loss of function fits with the phenotype of the family. In particular, the proband, a woman displaying the highest BMD (sum Z‐score = 7), carries both variants, whereas the other two affected members carry one each. VAV3 encodes a guanine‐nucleotide‐exchange factor with an important role in osteoclast activation and function. Although no previous cases of VAV3 mutations have been reported in humans, Vav3 knockout (KO) mice display dense bones, similarly to the high‐BMD phenotype present in our family. The ADGRE5 gene encodes an adhesion G protein‐coupled receptor expressed in osteoclasts whose KO mouse displays increased trabecular bone volume. Combined, these mouse and human data highlight VAV3 and ADGRE5 as novel putative high‐BMD genes with additive effects, and potential therapeutic targets for osteoporosis. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Genetic Analysis in a Familial Case With High Bone Mineral Density Suggests Additive Effects at Two Loci

et al. 2022

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“…Based on the inheritance pattern, monogenic diseases can be classified as recessive or dominant. These diseases have been extensively described in previous reviews ( 7 – 10 ). Below we will focus mainly on those musculoskeletal conditions where novel treatments have been developed.…”

Section: What Have We Learned From Monogenic Skeletal Disorders?mentioning

confidence: 94%

“…Genetic mutations affecting the SOST (chr17q12-21) gene lead to two similar syndromes: sclerosteosis and van Buchem disease, described in detail in previous reviews ( 10 , 40 , 41 ). Sclerosteosis arises from loss-of-function mutations within the SOST gene; whereas, van Buchem disease from deletion of a region (~52-kb) downstream of the SOST gene, which is relevant for proper gene expression ( 42 ).…”

Section: What Have We Learned From Monogenic Skeletal Disorders?mentioning

confidence: 98%

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders

Trajanoska

Rivadeneira

2020

Front. Endocrinol.

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Current genetic studies of monogenic and complex bone diseases have broadened our understanding of disease pathophysiology, highlighting the need for medical interventions and treatments tailored to the characteristics of patients. As genomic research progresses, novel insights into the molecular mechanisms are starting to provide support to clinical decision-making; now offering ample opportunities for disease screening, diagnosis, prognosis and treatment. Drug targets holding mechanisms with genetic support are more likely to be successful. Therefore, implementing genetic information to the drug development process and a molecular redefinition of skeletal disease can help overcoming current shortcomings in pharmaceutical research, including failed attempts and appalling costs. This review summarizes the achievements of genetic studies in the bone field and their application to clinical care, illustrating the imminent advent of the genomic medicine era.

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“…El síndrome de Camurati-Engelmann, también conocido como displasia diafisaria progresiva, es una enfermedad rara, autosómica dominante, con penetrancia incompleta y expresividad variable 1 , que se caracteriza por aumento de la masa ósea haciendo parte del grupo de las displasias óseas esclerosantes 2,3 . Fue descrita por primera vez en 1920 por Cockayne en un niño de 9 años, quien consideró estos hallazgos como una manifestación anormal de sífilis congénita 4 .…”

Section: Introductionunclassified

Presentación atípica de síndrome de CamuratiEngelmann en una paciente femenina colombiana. Reporte de caso

Zuluaga¹,

Restrepo²,

Bermúdez³

et al. 2021

Rev Medicas UIS

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El síndrome de Camurati-Engelmann, también conocido como displasia diafisaria progresiva, es una enfermedad rara, autosómica dominante y con una prevalencia de uno por cada millón de habitantes. Genera mutaciones del factor de crecimiento transformante beta, que participa en la proliferación ósea. Son frecuentes las manifestaciones osteomusculares y neurológicas, con escasas expresiones de laboratorio. El diagnóstico se basa en la clínica, los hallazgos radiológicos y la confirmación genética; el tratamiento se dirige al control sintomático y el pronóstico es incierto. La presente publicación tiene como objetivo compartir con la comunidad médica el tercer caso de síndrome de Camurati-Engelmann conocido en Colombia. Se trata de una paciente femenina de 33 años con cuadro clínico de distonías intensas y signos y síntomas característicos de este síndrome, cuyo diagnóstico fue confirmado por prueba molecular, encontrando la presencia de la variante patogénica p.Arg156Cys en el gen TGF-β1, con presentación de novo.

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Sclerosing bone dysplasias

Cited by 20 publications

References 139 publications

Genetic Analysis in a Familial Case With High Bone Mineral Density Suggests Additive Effects at Two Loci

Genetic Analysis in a Familial Case With High Bone Mineral Density Suggests Additive Effects at Two Loci

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders

Presentación atípica de síndrome de CamuratiEngelmann en una paciente femenina colombiana. Reporte de caso

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