Análise molecular de pacientes com holoprosencefalia

• Ano de defesa: 2015
• Autor(a) principal: Gamba, Bruno Faulin [UNESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Cerebro - Doenças; Sistema nervoso central - Anomalias; Anomalias humanas; Genetica molecular; Central nervous system - Abnormalities
• Link de acesso: http://hdl.handle.net/11449/139310; http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/06-06-2016/000865904.pdf

Craniofacial anomalies are skull development changes and face that may or may not be accompanied by structural malformations and / or functional CNS. These represent the fourth most common cause among the congenital anomalies in newborns, determining, among the patients, poor prognosis in most cases. Holoprosecephaly is a malformation of the central nervous system due to a fault in the division of right and left hemispheres of the brain. It is known that the etiology is multiple and complex. The HPE phenotype is variable including a continuous spectrum from severe manifestations involving abnormalities of the brain and face to clinically normal individuals. Genetics evidences are presented every year by groups studying holoprosencephaly and the genotype/phenotype remains a challenge for geneticists. We analyzed ADN samples from 124 patients with clinical diagnosis for holoprosencephaly. All ADNs samples were subjected to molecular analysis by MLPA technique ( SALSA® MLPA® KIT -B1 holoprosencephaly P187 and P036 SALSA® MLPA® KIT - Human telomere -E1 -3). Thus, we identified deletions / duplications in genes already described for HPE, such as: three deletions in the SHH gene, one deletion of the TGIF gene and one duplication in ZIC2 gene. Among the 124 samples, 26 ADN samples were selected for analysis by arrayCGH allowing the identification of microdeletions/microduplications in new chromosomal regions: 2p25.2 - p25.1, 2p21, 8p23.2, 10p15.3, 13q14.2 and Xq13.3. MLPA and arrayCGH are often used in research on the etiology of HPE, in that way the efficiency of these techniques, since the methodology used in this study allowed the identification of deletions / duplications in chromosome individuals studied, corroborating the literature and identinfy new chromosomal regions to be elucidated to understand the etiology of this disease