Lekárska genetika a diagnostika 1/2024
Genetic background of autism spectrum disorders – case report
Introduction: Autism is a neurodevelopmental disorder with unclear etiology, while a large share of genetic factors in the manifestation of the disease is assumed. At the Academic Center for Autism Research, in cooperation with Laboratory of Genomic Medicine, GHC GENETICS SK, we performed thirteen genetic diagnoses of children with autism using the whole-exome sequencing approach. Case: A six-year-old girl with a diagnosis of autism spectrum disorders, intellectual disability, and hyperactive syndrome and without somatofacial dysmorphic signs was clinically and genetically examined in the ambulance of medical genetic clinic, Institute of Medical Biology, Genetics and Clinical genetics, University Hospital Bratislava. Results of clinical-genetic examinations include a normal karyotype, negative microarray analysis of CNV variants, and an increase in the number of trinucleotide repeats in the FMR1 gene, which indicated a full mutation associated with FRAX syndrome. Whole-exome sequencing analysis revealed the presence of eight rare DNA variants in genes associated with diseases related to intellectual disabilities and/or autism, which were classified as variants with uncertain clinical effect. Conclusion: Genetic diagnosis in the presented case report leads to an unclear conclusion, as is the case in a relatively high percentage of children with autism spectrum disorders. In our set of 13 samples, we have detected a causal finding explaining the autism phenotype in only 8%. However, we assume that the combination of microarray analysis together with the approach of whole-exome sequencing as well as with the optimization of the protocol for the evaluation of the obtained data, concerning the latest knowledge from databases and literature, can contribute to increasing the detection of causal DNA variants in the case of patients with autism.
Keywords: autism, genetic diagnostics, WES analysis, phenotype variant filter, rare variant
