Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.
Clin Genet
; 92(4): 415-422, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28295210
ABSTRACT
BACKGROUND:
Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID).AIMS:
Identification of genomic disorders in DD/ID. MATERIALS ANDMETHODS:
We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs.RESULTS:
We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. DISCUSSION ANDCONCLUSION:
We show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deficiências do Desenvolvimento
/
Proteínas de Ligação a DNA
/
Variações do Número de Cópias de DNA
/
Deficiência Intelectual
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article