Camurati-Engelmann disease. Genetics and clinical manifestations with a review of the literature.

Rs, Sparkes; Graham, C. Benjamin

doi:10.1136/jmg.9.1.73

Cited by 94 publications

(63 citation statements)

References 28 publications

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“…The wide range of severity of the disease is well-recognized but still unexplained [Sparkes and Graham, 1972].…”

Section: Introductionmentioning

confidence: 99%

Progressive diaphyseal dysplasia: A three-generation family with markedly variable expressivity

Saraiva¹

1997

Am. J. Med. Genet.

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Progressive diaphyseal dysplasia was found in a 3-generation family including 18 affected individuals. We describe the clinical and radiographic manifestations in 6 of 18 patients with this autosomal-dominant bone dysplasia and the good symptomatic response to corticosteroid treatment in one of these. The variability of manifestations of the disease in this family and in others previously described seems to depend on the sex of the patient and the parental origin of the mutation. The patients with more severe symptoms are males who inherited an allele of paternal origin. We suggest that the progressive diaphyseal dysplasia gene has a function in endochondral bone formation and that its mutation is a dynamic one with repeat expansion enhanced in father-to-son transmission.

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“…The wide range of severity of the disease is well-recognized but still unexplained [Sparkes and Graham, 1972].…”

Section: Introductionmentioning

confidence: 99%

Progressive diaphyseal dysplasia: A three-generation family with markedly variable expressivity

Saraiva¹

1997

Am. J. Med. Genet.

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“…The existence of sporadic forms is disputed, since other asymptomatic family members may not have been screened radiologically (Sparkes and Graham 1972).…”

Section: Discussionmentioning

confidence: 99%

“…Weakness and muscle underdevelopment affect mainly the pelvic girdle and legs and cause a waddling gait. There may also be growth retardation, dry skin with reduced subcutaneous fat, flat feet, valgus ankle deformity, altered reflexes, exophthalmos, nystagmus, auditory impairment and splenomegaly (Lennon et al 1961;Wolf and Ford 1971;Sparkes and Graham 1972;Naveh et al 1984;Greenspan 1991).…”

Section: Discussionmentioning

confidence: 99%

Engelmann’s Disease

Grey

Wallace

Crone

1996

The Journal of Bone and Joint Surgery. British volume

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“…Radiologically, it is characterized by hyperostosis and sclerosis of the diaphyses of the long bones and sclerosis of the skull base. Patients suffer mainly from bone pain, muscle weakness, a waddling gait, and fatigue (18). Mutations in TGFB1 were found to underlie this bone disorder (19,20).…”

mentioning

confidence: 99%

Transforming Growth Factor-β1 Mutations in Camurati-Engelmann Disease Lead to Increased Signaling by Altering either Activation or Secretion of the Mutant Protein

Janssens¹,

Dijke²,

Ralston³

et al. 2003

Journal of Biological Chemistry

109

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Transforming growth factor-␤1 (TGF-␤1) is secreted as a latent precursor, consisting of a homodimer of the latency-associated peptide and the mature peptide. TGF␤-1 can only exert its many functions after going from this latent to an active state, in which the binding site of the mature peptide for its receptor is no longer shielded by the latency-associated peptide. We and others reported that mutations in TGFB1 cause CamuratiEngelmann disease, a rare bone disorder. Until now, seven mutations have been published. In this study, we investigate the effect of the LLL12-13ins, Y81H, R218C, H222D, and C225R mutations on the functioning of TGF-␤1 in vitro. A luciferase reporter assay specific for TGF-␤-induced transcriptional response with wild type and mutant TGF-␤1 constructs showed a positive effect of all mutations on TGF-␤1 activity. By way of enzymelinked immunosorbent assay, we found that in the R218C, H222D, and C225R mutant constructs, this effect is caused by an increase in active TGF-␤1 in the medium of transfected cells. The LLL12-13ins and Y81H mutations on the contrary have a profound effect on secretion; a decreased amount of TGF-␤1 is secreted, but the increased luciferase activity shows that the intracellular accumulation of (aberrant) TGF-␤1 can initiate an enhanced transcriptional response, suggesting the existence of an alternative signaling pathway. Our data indicate that the mutations in the signal peptide and latency-associated peptide facilitate TGF-␤1 signaling, thus causing Camurati-Engelmann disease.

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Camurati-Engelmann disease. Genetics and clinical manifestations with a review of the literature.

Cited by 94 publications

References 28 publications

Progressive diaphyseal dysplasia: A three-generation family with markedly variable expressivity

Progressive diaphyseal dysplasia: A three-generation family with markedly variable expressivity

Engelmann’s Disease

Transforming Growth Factor-β1 Mutations in Camurati-Engelmann Disease Lead to Increased Signaling by Altering either Activation or Secretion of the Mutant Protein

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