Estudo Citogenético-molecular e Clínico de uma família com onze portadores de monossomia 5p ou trissomia 5p em decorrência de uma translocação (5;15)(p13;p12)

• Ano de defesa: 2008
• Autor(a) principal: Carvalho, Acacia Fernandes Lacerda de [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/48912/001300002rv08
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Monossomia 5p; Sindrome do cri-du-chat; trissomia 5p; Translocação
• Link de acesso: http://repositorio.unifesp.br/handle/11600/9497

Introduction: Partial monosomy 5p (Cri du Chat syndrome) and partial trisomy 5p are clinically well characterized syndromes, with several cases described in the literature. This, however, is the first molecular-cytogenetic and clinical study with both syndromes present in the same family. We describe eleven alive affected individuals with partial 5p monosomy or trisomy resulting from a parental balanced translocation t(5;15)(p13;p12). Objectives: The objectives of this work were to identify cytogenetically and clinically the 5p monosomy and trisomy cases and the carriers of the balanced translocation in the family, to determine molecularly the breakpoint involved in the translocation, to evaluate the intrafamilial phenotypic variations, to establish a genotype-phenotype correlation in 5p monosomy and trisomy, and to provide genetic counseling to the family. Casuistic and methods: Four generations of a family were studied. Cytogenetic evaluation was performed on G- and NOR-banded cultured lymphocytes. The fluorescence in situ hybridization (FISH) technique with bacterial artificial chromosome (BAC) probes was used to determine the breakpoint on 5p. Results: Six individuals with partial 5p monosomy and five with partial 5p trisomy were identified, presenting the karyotypes 46,XX or XY,der(5)t(5;15)(p13;p12) and 46,XX or XY,der(15)t(5;15)(p13;p12), respectively. Seven carriers of the balanced translocation were identified, six of them with affected children. After using 12 BAC probes, the breakpoint was mapped to the region corresponding to BAC RP11-1079N14, at 5p13.3, resulting in a deletion or duplication of about 32 Mb in the studied patients. The intrafamilial clinical evaluation of the patients with 5p monosomy showed that they presented most of the characteristics described in the cat eye syndrome, whereas the patients with 5p trisomy displayed a greater clinical variability, compared to the cases from the literature. Conclusions: The study identified the individuals with 5p monosomy and trisomy and the carriers of the balanced translocation, thus enabling to provide genetic counseling to the family. The determination of the breakpoint and of the unbalanced chromosome segment made it possible to establish a more precise karyotype-phenotype correlation and to better characterize the partial 5p monosomy and trisomy syndromes.