Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct 9;10(4):160.
doi: 10.3390/jpm10040160.

Evaluation of Chromosome Microarray Analysis in a Large Cohort of Females with Autism Spectrum Disorders: A Single Center Italian Study

Sara Calderoni  1   2 , Ivana Ricca  3 , Giulia Balboni  4 , Romina Cagiano  1 , Denise Cassandrini  3 , Stefano Doccini  3 , Angela Cosenza  1 , Deborah Tolomeo  3   5 , Raffaella Tancredi  1 , Filippo Maria Santorelli  3 , Filippo Muratori  1   2
Affiliations

Evaluation of Chromosome Microarray Analysis in a Large Cohort of Females with Autism Spectrum Disorders: A Single Center Italian Study

Sara Calderoni et al. J Pers Med. .

Abstract

Autism spectrum disorders (ASD) encompass a heterogeneous group of neurodevelopmental disorders resulting from the complex interaction between genetic and environmental factors. Thanks to the chromosome microarray analysis (CMA) in clinical practice, the accurate identification and characterization of submicroscopic deletions/duplications (copy number variants, CNVs) associated with ASD was made possible. However, the widely acknowledged excess of males on the autism spectrum reflects on a paucity of CMA studies specifically focused on females with ASD (f-ASD). In this framework, we aim to evaluate the frequency of causative CNVs in a single-center cohort of idiopathic f-ASD. Among the 90 f-ASD analyzed, we found 20 patients with one or two potentially pathogenic CNVs, including those previously associated with ASD (located at 16p13.2 16p11.2, 15q11.2, and 22q11.21 regions). An exploratory genotype/phenotype analysis revealed that the f-ASD with causative CNVs had statistically significantly lower restrictive and repetitive behaviors than those without CNVs or with non-causative CNVs. Future work should focus on further understanding of f-ASD genetic underpinnings, taking advantage of next-generation sequencing technologies, with the ultimate goal of contributing to precision medicine in ASD.

Keywords: Array-Comparative Genomic Hybridization (Array-CGH); autism spectrum disorders; copy number variants; females.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Graphical representation of chromosome microarray analysis (CMA) results in our group of 90 females affected by autism. In the pie chart is depicted the percentage of individuals with causative copy number variants (C-CNVs), non-causative copy number variants (N-CNVs) or without copy number variants (w-CNVs).
Figure 2
Figure 2
Bioinformatic analyses performed on ASD-candidate genes encompassed by C-CNVs. (A) A Core analysis run in Variant Effects Analysis mode using the Ingenuity Pathway Analysis software figured out cellular processes related to our gene dataset (21 genes) generating a functional network encompassing 11 genes (in red). Synaptic transmission resulted the most significant functional annotation (p-value 6.05 × 10−9). Bridging nodes (in white) were denoted evaluating both direct and indirect interactions related only to neurological diseases and with stringent level of confidence (B). Gene ontology (GO) categorization was carried out using ToppGene Suite. Top three ontologies for Molecular Function (dark grey) and Cellular Component (light grey) were annotated; statistical significance of GO terms was reported as −log10 (p-value). The number of genes belonging to each category was reported on the right of each bar.
See this image and copyright information in PMC

References

    1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders (DSM-5®) American Psychiatric Publication; Washington, DC, USA: 2013.
    1. Muhle R.A., Reed H.E., Stratigos K.A., Weele J.V.-V. The Emerging Clinical Neuroscience of Autism Spectrum Disorder: A Review. JAMA Psychiatry. 2018;75:514–523. doi: 10.1001/jamapsychiatry.2017.4685. - DOI - PubMed
    1. Kim J.Y., Son M.J., Son C.Y., Radua J., Eisenhut M., Gressier F., Koyanagi A., Carvalho A.F., Stubbs B., Solmi M., et al. Environmental risk factors and biomarkers for autism spectrum disorder: An umbrella review of the evidence. Lancet Psychiatry. 2019;6:590–600. doi: 10.1016/S2215-0366(19)30181-6. - DOI - PubMed
    1. Maenner M.J., Shaw K.A., Baio J., Washington A., Patrick M., DiRienzo M., Christensen D.L., Wiggins L.D., Pettygrove S., Andrews J.G., et al. Prevalence of Autism Spectrum Disorder among Children Aged 8 Years—Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016. MMWR Surveill. Summ. 2020;69:1–12. doi: 10.15585/mmwr.ss6904a1. - DOI - PMC - PubMed
    1. Narzisi A., Posada M., Barbieri F., Chericoni N., Ciuffolini D., Pinzino M., Romano R., Scattoni M.L., Tancredi R., Calderoni S., et al. Prevalence of Autism Spectrum Disorder in a large Italian catchment area: A school-based population study within the ASDEU project. Epidemiol. Psychiatr. Sci. 2018;29:e5. doi: 10.1017/S2045796018000483. - DOI - PMC - PubMed

LinkOut - more resources