Pharmacogenomics and Personalized Medicine (Jul 2022)

Multiple Recurrent Copy Number Variations (CNVs) in Chromosome 22 Including 22q11.2 Associated with Autism Spectrum Disorder

  • Alhazmi S,
  • Alzahrani M,
  • Farsi R,
  • Alharbi M,
  • Algothmi K,
  • Alburae N,
  • Ganash M,
  • Azhari S,
  • Basingab F,
  • Almuhammadi A,
  • Alqosaibi A,
  • Alkhatabi H,
  • Elaimi A,
  • Jan M,
  • Aldhalaan HM,
  • Alrafiah A,
  • Alrofaidi A

Journal volume & issue
Vol. Volume 15
pp. 705 – 720

Abstract

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Safiah Alhazmi,1 Maryam Alzahrani,1 Reem Farsi,1 Mona Alharbi,1 Khloud Algothmi,1 Najla Alburae,1 Magdah Ganash,1 Sheren Azhari,1 Fatemah Basingab,1 Asma Almuhammadi,1 Amany Alqosaibi,2 Heba Alkhatabi,3,4 Aisha Elaimi,3,4 Mohammed Jan,5 Hesham M Aldhalaan,6 Aziza Alrafiah,4 Aisha Alrofaidi1 1Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Biology, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia; 3Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Medical Laboratory Science, King Abdulaziz University, Jeddah, Saudi Arabia; 5College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 6Center for Autism Research at King Faisal Specialist Hospital & Research Center, Riyadh, Saudi ArabiaCorrespondence: Aziza Alrafiah, Department of Medical Laboratory Science, King Abdulaziz University, P.O Box 80200, Jeddah, 21589, Saudi Arabia, Tel +966 126401000 Ext. 23495, Fax +966 126401000 Ext. 21686, Email [email protected]: Autism spectrum disorder (ASD) is a developmental disorder that can cause substantial social, communication, and behavioral challenges. Genetic factors play a significant role in ASD, where the risk of ASD has been increased for unclear reasons. Twin studies have shown important evidence of both genetic and environmental contributions in ASD, where the level of contribution of these factors has not been proven yet. It has been suggested that copy number variation (CNV) duplication and the deletion of many genes in chromosome 22 (Ch22) may have a strong association with ASD. This study screened the CNVs in Ch22 in autistic Saudi children and assessed the candidate gene in the CNVs region of Ch22 that is most associated with ASD.Methods: This study included 15 autistic Saudi children as well as 4 healthy children as controls; DNA was extracted from samples and analyzed using array comparative genomic hybridization (aCGH) and DNA sequencing.Results: The aCGH detected (in only 6 autistic samples) deletion and duplication in many regions of Ch22, including some critical genes. Moreover, DNA sequencing determined a genetic mutation in the TBX1 gene sequence in autistic samples. This study, carried out using aCGH, found that six autistic patients had CNVs in Ch22, and DNA sequencing revealed mutations in the TBX1 gene in autistic samples but none in the control.Conclusion: CNV deletion and the duplication of the TBX1 gene could be related to ASD; therefore, this gene needs more analysis in terms of expression levels.Keywords: autism spectrum disorder, chromosome 22, copy number variations, Saudi autistic children, TBX1

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