Cultura e desenvolvimento humano sustentável

A cultura é cada vez mais o centro das políticas locais, pela importância que vem revelando no contexto de um paradigma de desenvolvimento humano integral. Para além da atenção que lhe é dirigida graças à sua intima conexão a fatores de índole económica, social e urbana; a sua relevância deve-se essencialmente às relações intrínsecas que mantém com as questões da identidade, da memória, da criatividade, da ciência e do pensamento e conhecimento crítico. Optámos por dividir este livro em três capítulos de modo a permitir uma sequência de leitura, desde as temáticas gerais de grande escala – da União Europeia e da Globalização, até ao cerne do problema que em nosso entendimento urge solucionar nas cidades: a efetiva e definitiva integração da dimensão cultural nas estratégias territoriais de desenvolvimento humano sustentável.N/

Maternally Inherited Partial Monosomy 9p (pter→p24.1) And Partial Trisomy 20p (pter→p12.1) Characterized By Microarray Comparative Genomic Hybridization

We report on a 17-year-old patient with midline defects, ocular hypertelorism, neuropsychomotor development delay, neonatal macrosomy, and dental anomalies. DNA copy number investigations using a Whole Genome TilePath array consisting, of 30K BAC/PAC clones showed a 6.36Mb deletion in the 9p24.1-p24.3 region and a 14.83Mb duplication in the 20p12.1-p13 region, which derived from a maternal balanced t(9;20)(p24.1;p12.1) as shown by FISH studies. Monosomy 9p is a well-delineated chromosomal syndrome with characteristic clinical features, while chromosome 20p duplication is a rare genetic condition. Only a handful of cases of monosomy 9/trisomy 20 have been previously described. In this report, we compare the phenotype of our patient with those already reported in the literature, and discuss the role of DMRT, DOCK8, FOXD4, VLDLR, RSPO4, AVP, RASSF2, PROKR2, BMP2, MKKS, and JAG1, all genes mapping to the deleted and duplicated regions. © 2011 Wiley Periodicals, Inc.1551127542761Alfi, O., Donnell, G.N., Crandall, B.F., Derencsenyi, A., Menon, R., Deletion of the short arm of chromosome #9 (46,9p-): A new deletion syndrome (1973) Ann Genet, 16, pp. 17-22Araújo, M., Sanches, M.R., Suzuki, L.A., Guerra, J.R.G., Farah, S.B., Mello, M.P., Molecular analysis of CYP21 and C4 genes in Brazilian families with the classical form of steroid 21-hydroxylase deficiency (1996) Braz J Med Biol Res, 29, pp. 1-13Barbaro, M., Balsamo, A., Anderlid, B.M., Myhre, A.G., Gennari, M., Nicoletti, A., Pittalis, M.C., Wedell, A., Characterization of deletions at 9p affecting the candidate regions for sex reversal and deletion 9p syndrome by MLPA (2009) Eur J Hum Genet, 17, pp. 1439-1447Bardoni, B., Zanaria, E., Guioli, S., Floridia, G., Worley, K.C., Tonini, G., Ferrante, E., Camerino, G., A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal (1994) Nat Genet, 7, pp. 497-501Bennett, C.P., Docherty, Z., Robb, S.A., Ramani, P., Hawkins, J.R., Grant, D., Deletion 9p and sex reversal (1993) J Med Genet, 30, pp. 518-520Centerwall, W., Francke, U., Familial trisomy 20p five cases and two carriers in three generations a review (1977) Ann Genet, 20, pp. 77-83Chaabouni, M., Turleau, C., Karboul, L., Jemaa, L.B., Maazoul, F., Attié-Bitach, T., Romana, S., Chaabouni, H., De novo trisomy 20p of paternal origin (2007) Am J Med Genet Part A, 143 A, pp. 1100-1103Chen, H., An approach to work-up of dysmorphic patients: Clinical, cytogenetic, and molecular aspects (1994) Keio J Med, 43, pp. 98-107Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER): Database of Genomic Variants (DGV): Ensembl C Genome Browser: European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations (ECARUCA)Fiegler, H., Redon, R., Andrews, D., Scott, C., Andrews, R., Carder, C., Clark, R., Carter, N.P., Accurate and reliable high-throughput detection of copy number variation in the human genome (2006) Genome Res, 16, pp. 1566-1574Funderburk, S.J., Sparkes, R.S., Sparkes, M.C., Trisomy 20p due to a paternal reciprocal translocation (1983) Ann Genet, 26, pp. 94-97Gil-da-Silva-Lopes, V.L., (1997) Malformação Frontonasal: estudo genético-clínico de 31 pacientes não portadors de quadros sindrômicos já definidos, , Campinas: Tese de Doutorado, Universidade Estadual de CampinasGil-da-Silva-Lopes, V.L., Maciel-Guerra, A.T., A clinical study of 31 individuals with midline facial defects with hypertelorism and a guideline for follow-up (2007) Arq Neuropsiquiatr, 65, pp. 396-401Grammatico, P., Cupilari, F., Di Rosa, C., Falcolini, M., Del Porto, G., 20p Duplication as a result of parental translocation: Familial case report and a contribution to the clinical delineation of the syndrome (1992) Clin Genet, 41, pp. 285-289Guion-Almeida, M.L., (2000) Hipertelorismo e defeitos de linha média facial: Estudo genético-clínico de uma amostra de pacientes, , Campinas: Tese de Doutorado, Universidade Estadual de CampinasHauge, X., Raca, G., Cooper, S., May, K., Spiro, R., Adam, M., Martin, C.L., Detailed characterization of, and clinical correlations in, 10 patients with distal deletions of chromosome 9p (2008) Genet Med, 10, pp. 599-611Hoo, J.J., Fischer, A., Fuhrmann, W., Familial tiny 9p/20p translocation: 9p24 the critical segment for monosomy 9p syndrome (1982) Ann Genet, 25, pp. 249-252Huret, J.L., Leonard, C., Forestier, B., Rethoré, M.O., Lejeune, J., Eleven new cases of del(9p) and features from 80 cases (1988) Med J Genet, 25, pp. 741-749Kirkpatrick, S.J., Pauli, R.M., Frontonasal malformation and deletion of 22q11 (1998) Am J Med Genet, 75, pp. 443-444Marcus, E.S., 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Maternally Inherited Partial Monosomy 9p (pter -> p24.1) and Partial Trisomy 20p (pter -> p12.1) Characterized by Microarray Comparative Genomic Hybridization

Genetics of disease, diagnosis and treatmen

Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation

Autism and mental retardation (MR) are often associated, suggesting that these conditions are etiologically related. Recently, array-based comparative genomic hybridization (array CGH) has identified submicroscopic deletions and duplications as a common cause of MR, prompting us to search for such genomic imbalances in autism. Here we describe a 1.5-Mb duplication on chromosome 16p13.1 that was found by high-resolution array CGH in four severe autistic male patients from three unrelated families. The same duplication was identified in several variably affected and unaffected relatives. A deletion of the same interval was detected in three unrelated patients with MR and other clinical abnormalities. In one patient we revealed a further rearrangement of the 16p13 imbalance that was not present in his unaffected mother. Duplications and deletions of this 1.5-Mb interval have not been described as copy number variants in the Database of Genomic Variants and have not been identified in >600 individuals from other cohorts examined by high-resolution array CGH in our laboratory. Thus we conclude that these aberrations represent recurrent genomic imbalances which predispose to autism and/or MR

Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.

The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high-resolution genome analyses in patients with unexplained mental retardation. Here we report the molecular and/or clinical characterization of 22 individuals with the 17q21.31 microdeletion syndrome. We estimate the prevalence of the syndrome to be 1 in 16,000 and show that it is highly underdiagnosed. Extensive clinical examination, reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behavior are the most characteristic features. Other clinically important features include epilepsy, heart defects (ASD, VSD), and kidney/ urologic anomalies. Using high-resolution oligonucleotide arrays, we narrow the 17q21.31 critical region to a 424-kb genomic segment (chr17: 41046729-41470954, hg17), encompassing at least six genes, among which the gene encoding microtubule-associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease-associated variants. In five deletion carriers, we identify a <500-bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined, the parent originating the deletion carries a common 900-kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p<10-5). Our data establishes the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognizable genomic disorder