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Observational Study
. 2019 Aug;7(8):e786.
doi: 10.1002/mgg3.786. Epub 2019 Jun 29.

Identification of rare copy number variations reveals PJA2, APCS, SYNPO, and TAC1 as novel candidate genes in Autism Spectrum Disorders

Tania Bitar  1   2 , Walid Hleihel  2 , Sylviane Marouillat  1 , Sandrine Vonwill  1   3 , Marie-Laure Vuillaume  1   3 , Michel Soufia  4 , Patrick Vourc'h  1   3 , Frederic Laumonnier  1 , Christian R Andres  1   3
Affiliations
Observational Study

Identification of rare copy number variations reveals PJA2, APCS, SYNPO, and TAC1 as novel candidate genes in Autism Spectrum Disorders

Tania Bitar et al. Mol Genet Genomic Med. 2019 Aug.

Abstract

Background: There is a strong evidence for genetic factors as the main causes of Autism Spectrum Disorders (ASD). To date, hundreds of genes have been identified either by copy number variations (CNVs) and/or single nucleotide variations. However, despite all the findings, the genetics of these disorders have not been totally explored.

Methods: Thus, the aim of our work was to identify rare CNVs and genes present in these regions in ASD children, using a high-resolution comparative genomic hybridization technique and quantitative PCR (qPCR) approach.

Results: Our results have shown 60-70 chromosomal aberrations per patient. We have initially selected 66 CNVs that have been further assessed using qPCR. Finally, we have validated 22 CNVs including 11 deletions and 11 duplications. Ten CNVs are de novo, 11 are inherited and one of unknown origin of transmission. Among the CNVs detected, novel ASD candidate genes PJA2, SYNPO, APCS, and TAC1 have been identified in our group of Lebanese patients. In addition, previously described CNVs have been identified containing genes such as SHANK3, MBP, CHL1, and others.

Conclusion: Our study broadens the population spectrum of studied ASD patients and adds new candidates at the list of genes contributing to these disorders.

Keywords: APCS; PJA2; SYNPO; TAC1; Autism Spectrum Disorders; CGHarray; copy number variations.

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Conflict of interest statement

The authors declare that they have no conflict of interests.

Figures

Figure 1
Figure 1
Synthesis of the results obtained by microarray CGH and qPCR
Figure 2
Figure 2
Pathway studio analysis of the four novel candidate genes. A biological network was created connecting genes with their biological functions. Red color represents the novel candidate genes, yellow colors for cellular process and the blue frames represent the functions related to neurodevelopment and synaptic functions
See this image and copyright information in PMC

References

    1. Armstrong, L. , Tarailo‐Graovac, M. , Sinclair, G. , Seath, K. I. , Wasserman, W. W. , Ross, C. J. , & van Karnebeek, C. D. M. (2017). A girl with developmental delay, ataxia, cranial nerve palsies, severe respiratory problems in infancy‐Expanding NDST1 syndrome. American Journal of Medical Genetics. Part A, 173(3), 712–715. 10.1002/ajmg.a.37621 - DOI - PubMed
    1. Bitar, T. , Mavel, S. , Emond, P. , Nadal‐Desbarats, L. , Lefèvre, A. , Mattar, H. , … Andres, C. R. (2018). Identification of metabolic pathway disturbances using multimodal metabolomics in autistic disorders in a Middle Eastern population. Journal of Pharmaceutical and Biomedical Analysis, 152, 57–65. 10.1016/j.jpba.2018.01.007 - DOI - PubMed
    1. Chen, C.‐H. , Chen, H.‐I. , Chien, W.‐H. , Li, L.‐H. , Wu, Y.‐Y. , Chiu, Y.‐N. , … Gau, S.‐F. (2017). High resolution analysis of rare copy number variants in patients with autism spectrum disorder from Taiwan. Scientific Reports, 7(1), 11919 10.1038/s41598-017-12081-4 - DOI - PMC - PubMed
    1. Giovedí, S. , Corradi, A. , Fassio, A. , & Benfenati, F. (2014). Involvement of synaptic genes in the pathogenesis of autism spectrum disorders: The case of synapsins. Frontiers in Pediatrics, 2, 94 10.3389/fped.2014.00094 - DOI - PMC - PubMed
    1. Glessner, J. T. , Wang, K. , Cai, G. , Korvatska, O. , Kim, C. E. , Wood, S. , … Hakonarson, H. (2009). Autism genome‐wide copy number variation reveals ubiquitin and neuronal genes. Nature, 459(7246), 569–573. 10.1038/nature07953 - DOI - PMC - PubMed

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