Diagnostic efficacy and new variants in isolated and complex autism spectrum disorder using molecular karyotyping
| Autor: | Barbara Gnidovec Stražišar, Sara Bertok, Luca Lovrečić, Maja Jekovec Vrhovšek, Marija Volk, Damjan Osredkar, Polona Rajar, Borut Peterlin |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine DNA Copy Number Variations genetic structures Microarray Autism Spectrum Disorder Cell Adhesion Molecules Neuronal Ubiquitin-Protein Ligases Vesicular Transport Proteins Muscle Proteins Biology 03 medical and health sciences mental disorders Intellectual disability Genetics medicine Humans Heritability of autism Genetic Testing Copy-number variation Child Oligonucleotide Array Sequence Analysis Genetic testing medicine.diagnostic_test Calcium-Binding Proteins Membrane Proteins General Medicine medicine.disease Human genetics Phenotype 030104 developmental biology Autism spectrum disorder Child Preschool Karyotyping Female CADPS2 |
| Zdroj: | Journal of Applied Genetics. 59:179-185 |
| ISSN: | 2190-3883 1234-1983 |
| DOI: | 10.1007/s13353-018-0440-y |
| Popis: | Autism spectrum disorder (ASD) is a group of the neurodevelopment disorders presenting as an isolated ASD or more complex forms, where a broader clinical phenotype comprised of developmental delay and intellectual disability is present. Both the isolated and complex forms have a significant causal genetic component and submicroscopic genomic copy number variations (CNV) are the most common identifiable genetic factor in these patients. The data on microarray testing in ASD cohorts are still accumulating and novel loci are often identified; therefore, we aimed to evaluate the diagnostic efficacy of the method and the relevance of implementing it into routine genetic testing in ASD patients. A genome-wide CNV analysis using the Agilent microarrays was performed in a group of 150 individuals with an isolated or complex ASD. Altogether, 11 (7.3%) pathogenic CNVs and 15 (10.0%) variants of unknown significance (VOUS) were identified, with the highest proportion of pathogenic CNVs in the subgroup of the complex ASD patients (14.3%). An interesting case of previously unreported partial UPF3B gene deletion was identified among the pathogenic CNVs. Among the CNVs with unknown significance, four VOUS involved genes with possible correlation to ASD, namely genes SNTG2, PARK2, CADPS2 and NLGN4X. The diagnostic efficacy of aCGH in our cohort was comparable with those of the previously reported and identified an important proportion of genetic ASD cases. Despite the continuum of published studies on the CNV testing in ASD cohorts, a considerable number of VOUS CNVs is still being identified, namely 10.0% in our study. |
| Databáze: | OpenAIRE |
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