Aumento na taxa de diagnóstico genético dos pacientes a partir da identificação de CNVs, por CMA, envolvendo genes implicados com a manifestação clínica da deficiência intelectual
Nenhuma Miniatura disponível
Data
2019-05-27
Autores
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Goiás
Resumo
Intellectual disability (ID) is characterized by significant impairment in both cognitive and
adaptive functions, originating before the age of 18 years. In addition, it is a common
phenotype sign in a cluster of heterogeneous syndromic or non-syndromic disorders,
associated with some comorbidities such as autism and congenital malformations. In the
worldwide, ID affects around 1–3% of the general population and in Brazil ID affects
approximately 0.8% of the population. The Copy number variations account for about 15–
20% of children with unexplained ID, compromising the functioning of several genes, with
more than 1,416 genes described as causative of this phenotype sign. The aim of the study
was to evaluate the occurrence of CNVs, identified by CMA with the size filter of < 100 kb,
harboring genes functionally associated with ID in patients from SUS with a clinical diagnosis
of ID referred for the genetic diagnosis. During January 2013 to December 2016, GTG
banding karyotype was performed in 325 patients with ID, achieve the genetic diagnostic in
57.2%, demonstrating to be an important screening approach for patients with DI. However,
42,8% of the patients showed the karyotype with no visible numerical or structural
alterations. The CMA analysis with the size filter of ≥ 100 kb was performed in these patients,
where it was possible to elucidate the genetic diagnose in 29.8% of the patients,
demonstrating 7,1 % of the increment on the diagnostic. All the cases remained without a
diagnosis were submitted to the CMA analysis with size filter of < 100 kb, where it was
identified loss CNVs in regions harboring CNTNAP2, FGF13, MID1, MID2, SHANK3, IL1RAPL1,
DMD, and PAK3 genes. The reduction of the size filter demonstrated an increase of 12% in the
ratio of diagnosis, expanding the spectrum of CNVs identification in regions which harboring
genes related to the clinical manifestation of ID. The application of both GTG banding and
CMA with the size filter of ≥ 100 kb and later the size filter of < 100 kb allowed an increase in
the genetic diagnosis of ID and comorbidities, giving a broad understanding of the genetic
aspects related to these conditions and allowing the adequate management of families.
Finally, the genetic counseling provides a better understanding of the genetic causes of ID,
the familial implications of the genetic contribution and the chance of recurrence.
Descrição
Palavras-chave
Citação
PINTO, Irene Plaza. Aumento na taxa de diagnóstico genético dos pacientes a partir da identificação de CNVs, por CMA, envolvendo genes implicados com a manifestação clínica da deficiência intelectual. 2019. 115 f. Tese (Doutorado em Biotecnologia e Biodiversidade em Rede Pró-Centro-Oeste) - Universidade Federal de Goiás, Goiânia, 2019.