Journal of Applied Genetics

, Volume 59, Issue 2, pp 179–185 | Cite as

Diagnostic efficacy and new variants in isolated and complex autism spectrum disorder using molecular karyotyping

  • Luca Lovrečić
  • Polona Rajar
  • Marija Volk
  • Sara Bertok
  • Barbara Gnidovec Stražišar
  • Damjan Osredkar
  • Maja Jekovec Vrhovšek
  • Borut Peterlin
Human Genetics • Original Paper


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.


Autism spectrum disorders ASD Microarrays Molecular karyotyping UPF3B gene Genetics of autism 



array comparative genomic hybridization


autism spectrum disorder(s)


copy number variant


variant of unknown significance


Authors’ contributions

LL, MV, SB, BGS, DO and MJV carried out the clinical evaluation and provided the clinical genetic consultations to patients. LL and PR analysed and interpreted the data. LL, PR, MV and BP drafted the manuscript. SB, BGS, MJV and DO critically revised the final manuscript. All authors read and approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study was approved by the National Ethical Review Board in Ljubljana, Slovenia (0120-288/2016-2). All participants (their legal representatives) signed a written, informed consent.


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Copyright information

© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2018

Authors and Affiliations

  1. 1.Clinical Institute of Medical GeneticsUniversity Medical Centre LjubljanaLjubljanaSlovenia
  2. 2.Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, Division of PaediatricsUniversity Medical Centre LjubljanaLjubljanaSlovenia
  3. 3.Department of Child, Adolescent and Developmental Neurology, Division of PaediatricsUniversity Medical Centre LjubljanaLjubljanaSlovenia

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