AUTORI: Lakatosova, S., Miklosovicova, M., Konecny, M., Wachsmannova, L., Krasnanska, G., Kopcikova, M., Kemenyova, P., Tomka, M., Lysiova, J., Ostatnikova, D., Repiska, G.
ABSTRAKT: Here, we present a case study of twin boys aged 2 and 7 years who both met the diagnostic criteria for autism spectrum disorders (ASDs) based on the standard diagnostic instruments ADOS-2 and ADI-R. Te clinical indication for genetic diagnostics in the frst boy was autism with high severity of symptoms, delayed speech development, and mild facial dysmorphia. Te second boy’s indication was autism with moderate severity of symptoms, delayed speech development, mild facial features, slowed psychomotor development, and microcephaly. Te microarray-based analysis of chromosome aberrations revealed a heterozygous 977,456 bp deletion of region 10q26.3 in both boys. Te region includes 28 genes, some of these genes are important in the development of the central nervous and urogenital systems, and heterozygous deletions in this region have been associated with mental retardation, growth and development disorders, and craniofacial anomalies. Te whole exome sequencing confrmed the presence of this deletion in both boys and, at the same time, led to the identifcation of a pathogenic SNV variant in the TRIO gene in the boy with microcephaly and delayed psychomotor development, which may explain the diferent phenotype of both boys. However, the segregation analysis of these variants in the family revealed that the microdeletion was inherited from the asymptomatic father, and the c.2149C> T variant in the TRIO gene was inherited from the asymptomatic mother, making the diagnostic fnding uncertain. Tis case highlights that when pathogenic or likely pathogenic variants are inherited from unafected parents, the clinical phenotype may result from a combined burden of multiple rare variants and polygenic risk, underscoring the importance of a comprehensive genomic analysis in complex cases. Tus, we emphasize the importance of utilizing available methods, such as whole exome sequencing besides microarray-based comparative genomic hybridization, in the genetic diagnosis of autism patients in Slovakia.