Clinical Phenotypes and ABCC6 Gene Mutations in Brazilian Families with Pseudoxanthoma Elasticum

NIH/NIAMSCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Dermatology FoundationUniversidade Federal de São Paulo, Dept Morphol & Genet, Div Genet, São Paulo, BrazilThomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Jefferson Med Coll, Philadelphia, PA 19107 USAThomas Jefferson Univ, Jefferson Inst Mol Med, Philadelphia, PA 19107 USAUniversidade Federal de São Paulo, Dept Morphol & Genet, Div Genet, São Paulo, BrazilNIH/NIAMS: R01AR28450-30Web of Scienc

Translocation (4;13) giving rise to different unbalances: duplication 4p and deletion 4p (Wolf-Hirschhorn Syndrome)

Objetivos: Investigacao de uma translocacao t(4;13)(p16;q11) presente em quatro geracoes de uma familia. Metodos: Avaliacao clinica e citogenetica dos diferentes membros da familia. Caracterizacao da translocacao por meio de tecnicas de citogenetica classica e molecular (FISH - Hibridacao in situ por fluorescencia). Correlacao dos cariotipos com as caracteristicas clinicas dos individuos portadores das translocacoes nao equilibradas. Estudo da segregacao da translocacao na familia para fins de aconselhamento genetico. Resultados: A proposita e seu pai, ambos com defiCiência mental moderada e desvios fenotipicos menores, compativeis com as caracteristicas da trissomia 4p, apresentam um cromossomo extra derivado de uma translocacao equilibrada t(4;13)(p16;q11) que foi observada na avo e bisavo da proposita. Seus cariotipos podem ser descritos como 47,XX (ou XY),+der(13)t(4;13)(p16;q11). 0 tio da proposita apresentava defiCiência mental grave e malformacoes multiplas compativeis com a Sindrome de Wolf-Hirschhorn. Seu cariotipo pode ser representado como 45,XY,der(4)t(4;13)(p16;q11)mat,-13. A FISH com sonda para a microdelecao 4p (regiao da Sindrome de Wolf-Hirschhorn) e sonda para a pintura cromossomica do cromossomos 4 comprovou que enquanto que a proposita e seu pai apresentam trissomia parcial 4p16-pter and 13pter-q11, o tio da proposita apresentava monossomia para esse segmento cromossomico. 0 desequilibrio do braco curto do cromossomo 13 nao acarreta efeito fenotipico significante. Conclusoes: A translocacao presente na familia revela aspectos bem interessantes. Um deles se refere a observacao de que a translocacao t(4;13)(p16;q11) equilibrada pode resultar em diferentes desequilibrios cromossomicos atraves de segregacao 3:1 terciaria. Ambos os gametas complementares originados por essa segregacao sao viaveis resultando nos pacientes com trissomia e monossomia 4p deste trabalho. Alem disso, o pai da proposita, que apresenta um cromossomo extra, era fertil, teve tres filhos tendo transmitido a mesma alteracao cromossomica para um deles (proposita). 0 aconselhamento genetico em casos de translocacoes reciprocas equilibradas deve ser unico para cada familia. Na presente familia, deve-se ter a preocupacao com o risco de transmissao do cromossomo extra da proposita, pois a alteracao mostrou-se compativel com a fertilidadeBV UNIFESP: Teses e dissertaçõe

Aneuploidy of chromosome 8 and C-MYC amplification in individuals from northern Brazil with gastric adenocarcinoma

Background: Gastric cancer is the third most frequent type of neoplasia. In northern Brazil, the State of Para has a high incidence of this type of neoplasia. Limited data are available so far on the genetic events involved in this disease. Materials and Methods: Dual-color fluorescence in situ hybridization (FISH) for the C-MYC gene and chromosome 8 centromere was performed in 11 gastric adenocarcinomas. Results: All cases showed aneuploidy of chromosome 8 and C-MYC amplification, in both the diffuse and the intestinal histopathological types of Lauren. No, correlation was found between polysomy 8 and the histopathological characteristics of the tumors. C-MYC amplification, like homogeneously-stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Translocation of C-MYC was observed only in the diffuse-type. Conclusion: Chromosome 8 can be used as a marker in the diagnosis of gastric adenocarcinoma. The C-WC oncogene requires further studies in order to verify if it is, when amplified, an etiological cause of transformation or a consequence of the proliferation process.Fed Univ Para, Ctr Ciencias Biol, Dept Biol, Lab Citogenet Humana & Genet Toxicol, BR-66075900 Belem, Para, BrazilUniv Fed Sao Paulo, Dept Morphol, Discipline Genet, Sao Paulo, SP, BrazilFed Univ Para, Joao Barros Barreto Univ Hosp, Dept Pathol, Belem, Para, BrazilFed Univ Para, Joao Barros Barreto Univ Hosp, Surg Serv, Belem, Para, BrazilUniv Fed Sao Paulo, Dept Morphol, Discipline Genet, Sao Paulo, SP, BrazilWeb of Scienc

Juvenile Polyposis/Hereditary Hemorrhagic Telangiectasia Syndrome in an Adolescent With Complex Chromosomal Rearrangement and Intellectual Disability

Universidade Federal de São Paulo, Dept Morphol & Genet, BR-04023900 São Paulo, BrazilHosp Servidor Publ Estado São Paulo, Div Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gynecol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gynecol, BR-04023900 São Paulo, BrazilWeb of Scienc

Different Conformation of Two Supernumerary 18p Isochromosomes, One with a Concomitant Partial 18q Trisomy

The presence of a supernumerary 18p isochromosome is a rare chromosomal abnormality that results in 18p tetrasomy. This is a report on the clinical, cytogenetic and molecular findings of 2 non-related patients with a supernumerary 18p isochromosome. Both patients present some features of the 18p tetrasomy syndrome (strabismus, low-set ears, long and narrow fingers and toes), but additional characteristics were also observed. Cytogenetic analysis, FISH, MLPA and SNP array techniques showed that one of the isochromosomes is symmetric and monocentric, while the other is asymmetric and dicentric, yet resulting in a similar tetrasomy of the 18pter-18p10 region, followed by a partial 18q11.2 trisomy, an unprecedented finding in the literature. Copyright (C) 2012 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Morfol & Genet, Disciplina Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Unidade Genet, Inst Crianca, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Patol, Lab Citogenomica, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morfol & Genet, Disciplina Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Unidade Genet, Inst Crianca, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Patol, Lab Citogenomica, BR-04023900 São Paulo, BrazilFAPESP: 10/50737-1Web of Scienc

Cytogenomic characterization of an unexpected 17.6 Mb 9p deletion associated to a 14.8 Mb 20p duplication in a dysmorphic patient with multiple congenital anomalies presenting a normal G-banding karyotype

We describe a female patient with developmental delay, dysmorphic features and multiple congenital anomalies who presented a normal G-banded karyotype at the 550-band resolution. Array and multiplex-ligation probe amplification (MLPA) techniques identified an unexpected large unbalanced genomic aberration: a 17.6 Mb deletion of 9p associated to a 14.8 Mb duplication of 20p. The deleted 9p genes, especially CER1 and FREM1, seem to be more relevant to the phenotype than the duplicated 20p genes. This study also shows the relevance of using molecular techniques to make an accurate diagnosis in patients with dysmorphic features and multiple anomalies suggestive of chromosome aberration, even if on G-banding their karyotype appears to be normal. Fluorescence in situ hybridization (FISH) was necessary to identify a masked balanced translocation in the patient's mother, indicating the importance of associating cytogenetic and molecular techniques in clinical genetics, given the implications for patient management and genetic counseling. (C) 2012 Elsevier B.V. All rights reserved.FAPESP (Brazil) [10/50737-1]FAPESP (Brazil

Genomic alterations in diffuse-type gastric cancer as shown by high-resolution comparative genomic hybridization

Gastric adenocarcinoma is a serious public health concern, especially in northern Brazil. Gastric cancer call be subdivided into diffuse and intestinal types. Genetic imbalances in diffuse-type gastric cancer remain largely unknown. in the present study, we analyzed 24 advanced diffuse-type gastric cancer samples from northern Brazil subjects using high-resolution comparative genomic hybridization. We found chromosomal alterations in 75% of samples. in cancers with aneusomies, the mean genomic copy number alteration was 6.4. Losses of chromosome regions exceeded gains. the most frequent losses were located at chromosome regions 11q and 18q (five samples for each region), 1pq, 3q, 4q, 5q, 13q, and 14q (four samples), followed by 2pq, 7p, 9pq, 11p, and 16p (three Samples). Our results confirm that gastric cancer has a complex pattern of chromosomal alterations that call he clue to general chromosomal instability related to the advanced stage of gastric carcinogenesis. Loss of 11q and 18q were the most frequent chromosomal changes in diffuse-type gastric adenocarcinoma in individuals from northern Brazil. Frequent loss of 11q chromosome region in this gastric cancer may be peculiar among this population. (C) 2009 Elsevier Inc. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Morphol & Genet, Div Genet, BR-04023900 São Paulo, BrazilInst Biol Sci, Human Cytogenet Lab, BR-66075900 Belem, Para, BrazilJoao de Barros Barreto Univ Hosp, BR-66073000 Belem, Para, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, Div Genet, BR-04023900 São Paulo, BrazilWeb of Scienc