Copy number variants prioritization after array-CGH analysis – a cohort of 1000 patients
| Autor: | Patrícia Paiva, Fabiana Ramos, Ana Jardim, Eunice Matoso, Joaquim Sá, Marta Pinto, Francisco Caramelo, Isabel M. Carreira, Nuno Lavoura, Jorge M. Saraiva, Luís Pires, Cláudia Pais, Margarida Venâncio, Joana B. Melo, Lúcia Simões, Ana Beleza, Lina Ramos, Alexandra Mascarenhas, José Ferrão, Susana Isabel Ferreira |
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| Rok vydání: | 2015 |
| Předmět: |
Perturbação Autística
medicine.medical_specialty Learning difficulties Copy number variation (CNV) classification Intellectual disability Biology Biochemistry Gene duplication Genotype Genetics medicine Genetics(clinical) Clinical significance Copy-number variation Molecular Biology Genetics (clinical) Biochemistry medical Deficiência Intelectual Research Biochemistry (medical) Cytogenetics Autism spectrum disorders medicine.disease Human genetics Multiple congenital anomalies Molecular Medicine Autism Array comparative genomic hybridization (array-CGH) Anomalias Congénitas Múltiplas Comparative genomic hybridization |
| Zdroj: | Molecular Cytogenetics |
| ISSN: | 1755-8166 |
| DOI: | 10.1186/s13039-015-0202-z |
| Popis: | Background Array-based comparative genomic hybridization has been assumed to be the first genetic test offered to detect genomic imbalances in patients with unexplained intellectual disability with or without dysmorphisms, multiple congenital anomalies, learning difficulties and autism spectrum disorders. Our study contributes to the genotype/phenotype correlation with the delineation of laboratory criteria which help to classify the different copy number variants (CNVs) detected. We clustered our findings into five classes ranging from an imbalance detected in a microdeletion/duplication syndrome region (class I) to imbalances that had previously been reported in normal subjects in the Database of Genomic Variants (DGV) and thus considered common variants (class IV). Results All the analyzed 1000 patients had at least one CNV independently of its clinical significance. Most of them, as expected, were alterations already reported in the DGV for normal individuals (class IV) or without known coding genes (class III-B). In approximately 14 % of the patients an imbalance involving known coding genes, but with partially overlapping or low frequency of CNVs described in the DGV was identified (class IIIA). In 10.4 % of the patients a pathogenic CNV that explained the phenotype was identified consisting of: 40 class I imbalances, 44 class II de novo imbalances and 21 class II X-chromosome imbalances in male patients. In 20 % of the patients a familial pathogenic or potentially pathogenic CNV, consisting of inherited class II imbalances, was identified that implied a family evaluation by the clinical geneticists. Conclusions As this interpretation can be sometimes difficult, particularly if it is not possible to study the parents, using the proposed classification we were able to prioritize the multiple imbalances that are identified in each patient without immediately having to classify them as pathogenic or benign. |
| Databáze: | OpenAIRE |
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