O Papel da variação do número de cópias genômicas no fenótipo clínico de deficiência intelectual em uma coorte retrospectiva da rede pública de saúde do Estado de Goiás
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2014-03-31
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Universidade Federal de Goiás
Resumo
Intellectual disability is a signal comprising a set of clinically and genetically
heterogeneous disorders in which the development and/or function of the brain is
compromised. This deficiency is characterized by significant limitations both in
intellectual functioning and in adaptive behavior and is observed begins before 18 years
of age. It is characterized by a high degree of variable expression, and the expression of
a wide range of phenotypes, ranging from various genetic syndromes known to
characteristics non-syndromic and psychological and/or psychiatric disorders. The
etiology is still poorly understood and about half of the cases are unclear. In recent years,
the chromosomal analysis by microarray has revolutionized the evaluation of patients
with developmental delay or intellectual disability. By this method, the genome of a
patient is examined to detect gains or losses of genetic material that are usually too small
to be detected by chromosome banding studies. Genomic deletions and duplications have
an important role in characterizing genetic diseases, including many neurological
disorders and neural development. Identifying these changes may contribute to the
clinical management of affected individuals and assist their families, and furthermore,
can provide information on the processes of development and brain function. In this
context the main objective of this study was identified possible submicroscopic genomic
changes associated with intellectual disability, using a platform Chromosomal Microarray
high resolution in patients referred by doctors of public health from Goiás state and had
initially a normal karyotype. Thus 15 patients with intellectual disabilities were tested by
high resolution HD CytoScan Array (Affymetrix) tecnology which detected the presence
of 33 variations in the number of genome copies in 10 (66.7%) of the probands. Nineteen
microduplications (57.6%) and 14 microdeletions (42.4%) were observed, and 17 CNVs
(51.5%) were neutral, 7 (21.2%) pathogenic, 5 (15.15%) potentially pathogenic and 4
(12.12%) of uncertain significance. Five patients showed no change in the number of
copies. In this study, we could propose a genetic etiology for the phenotype of 8 patients
and thus the diagnostic yield of the platform used was 53.3%. Although modest, this study
was significant because this technology was first employed in the state of Goiás and thus,
could contribute more genetic information about this complex and heterogeneous
neurological sign of great importance to global public health.
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Pereira, Rodrigo Roncato. O Papel da variação do número de cópias genômicas no fenótipo clínico de deficiência intelectual em uma coorte retrospectiva da rede pública de saúde do Estado de Goiás. 2014. 118 f. Tese (Doutorado em Biologia) - Programa de Pós-graduação em Biologia (ICB) - Universidade Federal de Goiás, Goiânia, 2014.