Intrafamilial phenotypic variability in Engelmann disease (ED): Are ED and Ribbing disease the same entity?

Makita, Yoshio; Nishimura, Gen; Ikegawa, Shiro; Ishii, Takumi; Ito, Yoshiya; Okuno, Akimasa

doi:10.1002/(sici)1096-8628(20000313)91:2<153::aid-ajmg15>3.0.co;2-u

Cited by 49 publications

(27 citation statements)

References 10 publications

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“…All mutations investigated so far increase TGFb1 activity. 17 21 In CED patients, the narrowing of the *This family has been described by Janssens et al 12 ÀThis family has been described by Makita et al 9 These families have been described by Campos-Xavier et al 10 1This family has been described by Wallace et al…”

Section: Molecular Analysis and Pathogenesismentioning

confidence: 96%

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Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment

Janssens

Vanhoenacker

Bonduelle

et al. 2005

Journal of Medical Genetics

213

254

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Section: Molecular Analysis and Pathogenesismentioning

confidence: 96%

“…Data on 10 additional families (59 patients) were collected from published reports. [9][10][11][12] Including the families presented in this paper, TGFB1 mutations in 45 CED families have been described worldwide. 10 11 13-18 For the remaining 21 families, however, no published clinical or radiological information was available.…”

mentioning

confidence: 99%

Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment

Janssens

Vanhoenacker

Bonduelle

et al. 2005

Journal of Medical Genetics

213

254

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“…2C). This phenotype resembles the hyperosteosis associated with Camurati-Engelmann disease (26). Although the Mitf mi-ew protein acts in a strong dominant negative fashion in vitro (9), only a small fraction of the mutant protein translocates to the nucleus (27).…”

Section: Tfe3 and Tfec Mutations To Begin To Analyze The Functions Omentioning

confidence: 99%

Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development

Steingrı́msson

Tessarollo

Pathak

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

197

186

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The Mitf-Tfe family of basic helix-loop-helix-leucine zipper (bHLHZip) transcription factors encodes four family members: Mitf, Tfe3, Tfeb, and Tfec. In vitro, each protein in the family can bind DNA as a homo-or heterodimer with other family members. Mutational studies in mice have shown that Mitf is essential for melanocyte and eye development, whereas Tfeb is required for placental vascularization. Here, we uncover a role for Tfe3 in osteoclast development, a role that is functionally redundant with Mitf. Although osteoclasts seem normal in Mitf or Tfe3 null mice, the combined loss of the two genes results in severe osteopetrosis. We also show that Tfec mutant mice are phenotypically normal, and that the Tfec mutation does not alter the phenotype of Mitf, Tfeb, or Tfe3 mutant mice. Surprisingly, our studies failed to identify any phenotypic overlap between the different Mitf-Tfe mutations. These results suggest that heterodimeric interactions are not essential for Mitf-Tfe function in contrast to other bHLH-Zip families like Myc͞Max͞Mad, where heterodimeric interactions seem to be essential.

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“…Camurati-Engelmann disease (CED) or progressive diaphyseal dysplasia (DPD1) is an autosomal dominant disorder that is characterized by hyperosteosis and sclerosis of the diaphysis of the long bones (10). The onset of CED is often during early childhood with severe pain in the legs, muscle weakness, a waddling gait, and easy fatigability.…”

mentioning

confidence: 99%

Domain-specific Mutations of a Transforming Growth Factor (TGF)-β1 Latency-associated Peptide Cause Camurati-Engelmann Disease Because of the Formation of a Constitutively Active Form of TGF-β1

Saito¹,

Kinoshita²,

Yoshiura³

et al. 2001

Journal of Biological Chemistry

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Transforming growth factor (TGF)-␤1 is secreted as a latent form, which consists of its mature form and a latency-associated peptide (␤1-LAP) in either the presence or the absence of additional latent TGF-␤1-binding protein. We recently reported that three different missense mutations (R218H, R218C, and C225R) of ␤1-LAP cause the Camurati-Engelmann disease (CED), an autosomal dominant disorder characterized by hyperosteosis and sclerosis of the diaphysis of the long bones. Pulse-chase experiments using fibroblasts from CED patients and expression experiments of the mutant genes in an insect cell system suggest that these mutations disrupt the association of ␤1-LAP and TGF-␤1 and the subsequent release of the mature TGF-␤1. Furthermore, the cell growth of fibroblasts from a CED patient and mutant gene-transfected fibroblasts was suppressed via TGF-␤1. The growth suppression observed was attenuated by neutralizing antibody to TGF-␤1 or by treatment of dexamethasone. On the other hand, the proliferation of human osteoblastic MG-63 cells was accelerated by coculture with CED fibroblasts. These data suggest that the domain-specific mutations of ␤1-LAP result in a more facile activation of TGF-␤1, thus causing CED. Transforming growth factor-␤1 (TGF-␤1)1 is a multifunctional protein acting on cell growth, differentiation, and morphogenesis of many different-type cells. In skeletal tissue, TGF-␤1 serves as a systematic regulator that couples bone formation and resorption by regulating the function of the osteoblasts and osteoclasts (1-5).The mature form of TGF-␤1 is proteolytically cleaved from the N-terminal remnant of the TGF-␤1 precursor, designated as TGF-␤1 latency-associated peptide (␤1-LAP) but remains non-covalently associated with the rest of the complex, which plays a role in latency of TGF-␤1 (6). TGF-␤1 is ubiquitously distributed, and the activation of the latent form is likely an important step, because it exists as either a large latent form, composed of ␤1-LAP, TGF-␤1, and latent TGF-␤1-binding protein (LTBP), or a small latent form, which is devoid of LTBP (7). Under normal conditions, activation of the latent TGF-␤1 is strictly controlled as follows. The large latent form is temporarily converted to the small latent form, which is then cleaved by plasmin or the plasmin-like protease to give the mature TGF-␤1 (6, 8, 9).Camurati-Engelmann disease (CED) or progressive diaphyseal dysplasia (DPD1) is an autosomal dominant disorder that is characterized by hyperosteosis and sclerosis of the diaphysis of the long bones (10). The onset of CED is often during early childhood with severe pain in the legs, muscle weakness, a waddling gait, and easy fatigability. The patients occasionally suffer from systemic manifestations, such as anemia, leukopenia, or hepatosplenomegaly (11). We, as well as two other groups, previously assigned the locus for CED to chromosome 19q13. 1-q13.3 (12-14). By a positional candidate gene approach and haplotype analyses, three different missense mutations (R218H, R218C, and C225R), wh...

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Intrafamilial phenotypic variability in Engelmann disease (ED): Are ED and Ribbing disease the same entity?

Cited by 49 publications

References 10 publications

Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment

Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment

Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development

Domain-specific Mutations of a Transforming Growth Factor (TGF)-β1 Latency-associated Peptide Cause Camurati-Engelmann Disease Because of the Formation of a Constitutively Active Form of TGF-β1

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