Investigação de fatores genéticos na etiologia de fendas orofaciais típicas / Investigation of genetic factors on the etiology of orofacial clefts typical

AUTOR(ES)

Milena Simioni

FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

27/02/2012

RESUMO

Typical oral cleft (TOC) is a prevalent and heterogeneous group of congenital defects with multiple etiologies, which remain unknown in several cases. Population studies detected several genes related to TOC. An individualized investigation, involving different laboratorial tools at same time, is an approach that can contribute on the etiological characterization of the TOC. The aim of this study was to investigate genetic factors involved on TOC in a sample composed by 23 individuals (syndromic and non-syndromic; familial and sporadic cases). The control group included 20 individuals without TOC in three generations. All patients were previously evaluated by clinical geneticists and performed karyotype test that showed chromosomal aberrations in two cases. Copy number variation (CNV) investigation by genomic hibridization in arrays (aGH), based in a comparative to control group data, detected a new candidate gene to TOC (TCEB3), and identified a duplication affecting FGFR1 gene. In one patient with syndromic form of submucous cleft palate, the use of aGH technique, together with Fluorescent in situ hibridization (FISH) and Multiplex ligation-dependent probe amplification (MLPA), characterized the chromosomal aberration previously detected by karyotype. Direct sequencing of IRF6, FOXE1, GLI2, MSX2, SKI, SATB2, SPRY1, MSX1, FGF8 and FGFR1 genes was performed in all individuals; in a specific case, P63 gene was investigated. New sequence alterations were found in FOXE1, MSX1, GLI2 e FGF8 genes, as well as an insertion in P63 gene, which effects will be verified in futures studies. In conclusion, results here described reflect the diversity of genetic factors involved in the etiology of TOC and the type of study show the efficiency of the use of different techniques in the etiological investigation of this congenital defect.

ASSUNTO(S)

fenda labial fenda palatina anormalidades craniofaciais microarranjos de dna cleft of lip cleft palate craniofacial abnormalities microarrays dna

Documentos Relacionados

• Caracterização de aspectos relevantes para a avaliação genético-clínica de portadores de fendas orofaciais em Alagoas
• Implicações diagnósticas de defeitos associados em pacientes com fendas orofaciais típicas
• Cytogenetics investigation on orofacial cleft individuals and screening of informative cases for further studies
• Prevalence of orofacial clefts and social factors in Brazil
• Fatores preponderantes para a nutrição de indivíduos com fenda orofacial típica e propostas para seu manejo