Correlação genótipo-fenótipo de pacientes com translocação aparentemente balanceada entre os cromossomos 8 e 13, e dos membros da família do ramo paterno
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Data
2009-05-27
Autores
Segato, Rosimeire [UNIFESP]
Orientadores
Payão, Spencer Luiz Marques [UNIFESP]
Tipo
Dissertação de mestrado
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Introdução: As aberrações cromossômicas são responsáveis por grande parte das malformações congênitas, deficiência mental, abortos espontâneos, além de desempenhar um importante papel na patogenia do câncer. Estão classificadas em numéricas ou estruturais, sendo que estas últimas podem ser aparentemente balanceadas, quando não são detectadas perda ou ganho de material cromossômico, ou não balanceadas, onde o rearranjo produz perda ou ganho de material cromossômico, sendo responsável por grande variabilidade fenotípica. Objetivos: Considerando uma família cuja propósita é portadora de translocação, aparentemente balanceada, oriunda do pai, foram investigadas três gerações do ramo paterno e correlacionado genótipo/fenótipo dos indivíduos. Material e Métodos: A partir de cultura de sangue total foram realizadas as técnicas de bandamento GTG e Cariotipagem Espectral, SKY, no material obtido da propósita e os demais membros da família foram avaliados por bandamento GTG. Resultados: Dentre os resultados obtidos, o achado citogenético da propósita evidenciou cariótipo 46,XX,t(8;13)(q22;q32), com várias alterações fenotípicas e o cariótipo paterno com a mesma translocação; a análise citogenética materna apresentou translocação, aparentemente balanceada, 46,XX,t(3;16)(p21;p13); uma irmã da propósita apresentou ambas translocações: 46,XX,t(3;16)(p21;p13),t(8;13)(q22;q32); uma outra com a mesma translocação da mãe, 46,XX,t(3;16)(p21;p13), sendo todos fenotipicamente normais; um irmão e demais membros da família apresentaram cariótipo normal. O mecanismo de segregação responsável pelo cariótipo observado na propósita foi o alternado. Por se tratar de duas translocações importantes sendo segregadas, evento raríssimo na literatura, foi realizado o Aconselhamento Genético, apresentando os riscos para as futuras descendências, familiares e afetados com enfoque para indivíduos afetados em idade reprodutiva. Conclusão: Mediante análise citogenética dos indivíduos das três gerações, foi possível concluir que ocorreu um evento “de novo” transmitido à propósita e, através da técnica de SKY, foi confirmada a translocação oriunda do pai. Em virtude da propósita apresentar alterações fenotípicas importantes eseu pai ser normal fenotipicamente, fica evidente a ocorrência de uma instabilidade genômica caracterizada por uma provável microdeleção ou microduplicação, ou outro rearranjo não detectado no nível de resolução da técnica de SKY..
Purpose: The chromosomal aberrations are responsible for a great number of the congenital malformations, mental deficiency, spontaneous abortion, besides playing an important role in the cancer pathogeny. They are classified as numericals or structurals, whereas these latter ones, can be apparently balanced, when loss or gain of the chromosomal material are not detected, or non balanced, in which rearrangement result of the loss or gain of the chromosomal material, being accountable for a great phenotypical variability. Objectives: Considering a family whose propositus is a translocation carrier, apparently balanced, of the father, three generations from the father’s have been investigated, and thus, correlating the genotype/phenotype of each individual pertaining the father’s generation. Material and Methods: GTG-banding and Spectral Karyotyping (SKY) techniques have been carried out using the material obtained from the propositus and the other members of the family have been evaluated by means of GTG-banding. Results: Considering the obtained results the cytogenetic finding of the propositus has shown 46,XX,t(8;13)(q22;q32), associated with several phenotypical alterations and the father’s karyotype with the same translocation, the mother’s cytogenetic analysis showed apparently balanced translocation 46,XX,t(3;16)(p21;p13), one sister with both translocations 46,XX,t(3;16)(p21;p13),t(8;13)(q22;q32), another one with the same translocation from the mother 46,XX,t(3;16)(p21;p13), being all of them phenotypically normal; one brother and other members of the family have presented normal karyotype. The segregation mechanism responsible for the observed karyotype in the propositus was alternate. Because it refers to two important translocations being segregated, such occurrence is unusual finding in the literature. For that reason, the genetical counseling was carried out, which presented the risks for the future descent, including all the affected in reproductive age. Conclusions: Through the cytogenetic investigation of the three generations, we could conclude that “de novo” event occurred. Moreover, by means of SKY (Spectral Karyotyping) technique it was confirmed that the translocation to the propositus was transmitted through her father. Due to the propositus presenting important phenotypical alterations, and her father being phenotypically normal, it is clear that the occurrence of a characterized genomic instability was not detected by means of the SKY technique.
Purpose: The chromosomal aberrations are responsible for a great number of the congenital malformations, mental deficiency, spontaneous abortion, besides playing an important role in the cancer pathogeny. They are classified as numericals or structurals, whereas these latter ones, can be apparently balanced, when loss or gain of the chromosomal material are not detected, or non balanced, in which rearrangement result of the loss or gain of the chromosomal material, being accountable for a great phenotypical variability. Objectives: Considering a family whose propositus is a translocation carrier, apparently balanced, of the father, three generations from the father’s have been investigated, and thus, correlating the genotype/phenotype of each individual pertaining the father’s generation. Material and Methods: GTG-banding and Spectral Karyotyping (SKY) techniques have been carried out using the material obtained from the propositus and the other members of the family have been evaluated by means of GTG-banding. Results: Considering the obtained results the cytogenetic finding of the propositus has shown 46,XX,t(8;13)(q22;q32), associated with several phenotypical alterations and the father’s karyotype with the same translocation, the mother’s cytogenetic analysis showed apparently balanced translocation 46,XX,t(3;16)(p21;p13), one sister with both translocations 46,XX,t(3;16)(p21;p13),t(8;13)(q22;q32), another one with the same translocation from the mother 46,XX,t(3;16)(p21;p13), being all of them phenotypically normal; one brother and other members of the family have presented normal karyotype. The segregation mechanism responsible for the observed karyotype in the propositus was alternate. Because it refers to two important translocations being segregated, such occurrence is unusual finding in the literature. For that reason, the genetical counseling was carried out, which presented the risks for the future descent, including all the affected in reproductive age. Conclusions: Through the cytogenetic investigation of the three generations, we could conclude that “de novo” event occurred. Moreover, by means of SKY (Spectral Karyotyping) technique it was confirmed that the translocation to the propositus was transmitted through her father. Due to the propositus presenting important phenotypical alterations, and her father being phenotypically normal, it is clear that the occurrence of a characterized genomic instability was not detected by means of the SKY technique.
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Citação
SEGATO, Rosimeire. Correlação genótipo-fenótipo de pacientes com translocação aparentemente balanceada entre os cromossomos 8 e 13, e dos membros da família do ramo paterno. 2009. 74 f. Dissertação (Mestrado) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2009.