Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws followed by development of fibrous tissue masses, which causes a characteristic facial swelling. Here we describe seven mutations in the SH3-binding protein SH3BP2 (MIM 602104) on chromosome 4p16.3 that cause cherubism.

Craniometaphyseal dysplasia (CMD) is a rare skeletal disorder characterized by progressive thickening and increased mineral density of craniofacial bones and abnormally developed metaphyses in long bones. Linkage studies mapped the locus for the autosomal dominant form of CMD to an approximately 5-cM interval on chromosome 5p, which is defined by recombinations between loci D5S810 and D5S1954. Mutational analysis of positional candidate genes was performed, and we describe herein three different mutations, in five different families and in isolated cases, in ANK, a multipass transmembrane protein involved in the transport of intracellular pyrophosphate into extracellular matrix. The mutations are two in-frame deletions and one in-frame insertion caused by a splicing defect. All mutations cluster within seven amino acids in one of the six possible cytosolic domains of ANK. These results suggest that the mutated protein has a dominant negative effect on the function of ANK, since reduced levels of pyrophosphate in bone matrix are known to increase mineralization.

Cherubism is an autosomal dominant disorder that may be related to tooth development and eruption. It is a disorder of age-related bone remodeling, mostly limited to the maxilla and the mandible, with loss of bone in the jaws and its replacement with large amounts of fibrous tissue. We have used a genomewide search with a three-generation family and have established linkage to chromosome 4p16. Three other families affected with cherubism were also genotyped and were mapped to the same locus. The combined LOD score is 4.21 at a recombination fraction of 0, and the locus spans an interval of approximately 22 cM.

Craniometaphyseal dysplasia (CMD) is a rare sclerosing skeletal disorder with progressive hyperostosis of craniofacial bones. CMD can be inherited in an autosomal dominant (AD) trait or occur after de novo mutations in the pyrophosphate transporter ANKH. Although the autosomal recessive (AR) form of CMD had been mapped to 6q21-22 the mutation has been elusive. In this study, we performed whole-exome sequencing for one subject with AR CMD and identified a novel missense mutation (c.716G>A, p.Arg239Gln) in the C-terminus of the gap junction protein alpha-1 (GJA1) coding for connexin 43 (Cx43). We confirmed this mutation in 6 individuals from 3 additional families. The homozygous mutation cosegregated only with affected family members. Connexin 43 is a major component of gap junctions in osteoblasts, osteocytes, osteoclasts and chondrocytes. Gap junctions are responsible for the diffusion of low molecular weight molecules between cells. Mutations in Cx43 cause several dominant and recessive disorders involving developmental abnormalities of bone such as dominant and recessive oculodentodigital dysplasia (ODDD; MIM #164200, 257850) and isolated syndactyly type III (MIM #186100), the characteristic digital anomaly in ODDD. However, characteristic ocular and dental features of ODDD as well as syndactyly are absent in patients with the recessive Arg239Gln Cx43 mutation. Bone remodeling mechanisms disrupted by this novel Cx43 mutation remain to be elucidated.

Cherubism is a rare autosomal dominant fibro-osseous disorder that affects almost exclusively maxilla and mandible. Extracranial skeletal involvement is rare. We report on three affected males in three generations. The youngest affected relative was examined at age 4 months. He also had craniosynostosis. His affected father and grandfather had cherubism and clubbing of the fingers. Cherubism was mapped to region 4p16. Because of the associated cranio-synostosis, we excluded the FGFR3 gene as a candidate gene for cherubism.

Celso azzan Júnior. São Paulo: annablume, 2005. 107 p. 14 cm x 21 cm. [título original: L´immatériel: connaissance, valeur et capital]. apesar de o original ter sido publicado em 2003, esse livro de André Gorz é atual e necessário, particularmente diante dos desafios da crise da economia mundial em curso. Ele remete o leitor para reflexões relevantes sobre as relações de trabalho, o conhecimento e o capitalismo. a crise atual está gerando uma legião de desempregados, fenômeno de grande impacto observado especialmente nos EUa, no Japão, na Europa e em países emergentes, como o Brasil. a leitura de Gorz leva a crer que as demissões são decorrentes do subconsumo e também que estão vinculadas ao oportunismo do momento para resolver um problema que se arrasta há mais tempo: o capital precisa cada vez menos de trabalho de produção material. aliás, Gorz explicitamente prevê esta crise no capítulo II, quando afirma, também, que o capitalismo cognitivo é a crise do capitalismo. O autor, austríaco radicado na França, respeitado estudioso da sociedade contemporânea, assinou 16 obras, entre elas Misérias do presente, riqueza do possível (2004) e Crítica da divisão do trabalho (2001), ambas traduzidas para o português.

Cherubism is a rare autosomal dominant fibro-osseous disorder that affects almost exclusively maxilla and mandible. Extracranial skeletal involvement is rare. We report on three affected males in three generations. The youngest affected relative was examined at age 4 months. He also had craniosynostosis. His affected father and grandfather had cherubism and clubbing of the fingers. Cherubism was mapped to region 4p16. Because of the associated cranio-synostosis, we excluded the FGFR3 gene as a candidate gene for cherubism.

BackgroundThe number of oropharyngeal lesions caused by HPV (Human papillomavirus) has been increasing worldwide in the past years. In spite of the clinical relevance of HPV infection in the anogenital tract of HIV-positive patients, the relevance of oropharynx HPV infection in these patients is not clear. The aim of the present study was to detect HPV infection, and clinical and cytological changes in the oropharynx of HIV-positive patients.MethodsSamples collected from the oropharynx of 100 HIV-positive patients were subjected to hybrid capture (HC), conventional and liquid-based cytology. Clinical data were also collected to investigate the relation with HPV status.ResultsHigh and low-risk types of HPV were present in 8% and 16.7% of the total sample. The mean ± sd (maximum-minimum) of the relative ratio light unit (RLU)/cutoff (CO) was 2.94 ± 2.58 (1.09–7.87) and 1.61 ± 0.65 (1.07–2.8) for high- and low-risk-HPV, respectively. By cytology, dysplasia was not detected, but atypical squamous cells of undetermined significance (ASC-US) were diagnosed in two samples. No clinical change, suggestive of dysplasia/cancer, was detected.ConclusionOur study was able to detect and characterize HPV infection by hybrid capture, which may represent a good tool for screening and follow-up of HPV in the studied population. The frequency and viral load of HPV were low. Neither clinical nor cytological changes suggestive of dysplasia/neoplasia were observed in oropharynx of HIV-positive patients.