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

Overview

Journal Pharmgenomics Pers Med

Publisher Dove Medical Press

Date 2022 Jul 28

PMID 35898556

Authors

Safiah Alhazmi

Maryam Alzahrani

Reem Farsi

Mona Alharbi

Khloud Algothmi

Najla Alburae

Magdah Ganash

Sheren Azhari

Fatemah Basingab

Asma Almuhammadi

Amany Alqosaibi

Heba Alkhatabi

Aisha Elaimi

Mohammed Jan

Hesham M Aldhalaan

Aziza Alrafiah

Aisha Alrofaidi

Affiliations

Soon will be listed here.

Abstract

Introduction: 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.

Citing Articles

A cohort study of neurodevelopmental disorders and/or congenital anomalies using high resolution chromosomal microarrays in southern Brazil highlighting the significance of ASD.

Chaves T, Ocampos M, Barbato I, de Camargo Pinto L, de Luca G, Barbato Filho J Sci Rep. 2024; 14(1):3762.

PMID: 38355898 PMC: 10867078. DOI: 10.1038/s41598-024-54385-2.

Bioinformatics analysis of genomic and immune infiltration patterns in autism spectrum disorder.

Wei R, Guo W, Wu Y, Alarcon Rodriguez R, Mullor M, Gui Y Ann Transl Med. 2022; 10(18):1013.

PMID: 36267781 PMC: 9577768. DOI: 10.21037/atm-22-4108.

References

Geschwind D . Genetics of autism spectrum disorders. Trends Cogn Sci. 2011; 15(9):409-16. PMC: 3691066. DOI: 10.1016/j.tics.2011.07.003. View

Jaouadi A, Tabebi M, Abdelhedi F, Abid D, Kamoun F, Chabchoub I . A novel TBX1 missense mutation in patients with syndromic congenital heart defects. Biochem Biophys Res Commun. 2018; 499(3):563-569. DOI: 10.1016/j.bbrc.2018.03.190. View

Safari M, Ghafouri-Fard S, Noroozi R, Sayad A, Omrani M, Komaki A . FOXP3 gene variations and susceptibility to autism: A case-control study. Gene. 2016; 596:119-122. DOI: 10.1016/j.gene.2016.10.019. View

El Omari K, De Mesmaeker J, Karia D, Ginn H, Bhattacharya S, Mancini E . Structure of the DNA-bound T-box domain of human TBX1, a transcription factor associated with the DiGeorge syndrome. Proteins. 2011; 80(2):655-60. DOI: 10.1002/prot.23208. View

Grover D, Verma R, Goes F, Mahon P, Gershon E, McMahon F . Family-based association of YWHAH in psychotic bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2009; 150B(7):977-83. PMC: 3918450. DOI: 10.1002/ajmg.b.30927. View

Li X, Zou H, Brown W . Genes associated with autism spectrum disorder. Brain Res Bull. 2012; 88(6):543-52. DOI: 10.1016/j.brainresbull.2012.05.017. View

Wang H, Chen D, Ma L, Meng H, Liu Y, Xie W . Genetic analysis of the TBX1 gene promoter in ventricular septal defects. Mol Cell Biochem. 2012; 370(1-2):53-8. DOI: 10.1007/s11010-012-1397-5. View

Torrico B, Anton-Galindo E, Fernandez-Castillo N, Rojo-Francas E, Ghorbani S, Pineda-Cirera L . Involvement of the 14-3-3 Gene Family in Autism Spectrum Disorder and Schizophrenia: Genetics, Transcriptomics and Functional Analyses. J Clin Med. 2020; 9(6). PMC: 7356291. DOI: 10.3390/jcm9061851. View

Giovedi S, Corradi A, Fassio A, Benfenati F . Involvement of synaptic genes in the pathogenesis of autism spectrum disorders: the case of synapsins. Front Pediatr. 2014; 2:94. PMC: 4154395. DOI: 10.3389/fped.2014.00094. View

10.

McDonald-McGinn D, Sullivan K, Marino B, Philip N, Swillen A, Vorstman J . 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2016; 1:15071. PMC: 4900471. DOI: 10.1038/nrdp.2015.71. View

11.

Qin L, Ma K, Wang Z, Hu Z, Matas E, Wei J . Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibition. Nat Neurosci. 2018; 21(4):564-575. PMC: 5876144. DOI: 10.1038/s41593-018-0110-8. View

12.

Lindsay E, Vitelli F, Su H, Morishima M, Huynh T, Pramparo T . Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature. 2001; 410(6824):97-101. DOI: 10.1038/35065105. View

13.

Persico A, Napolioni V . Autism genetics. Behav Brain Res. 2013; 251:95-112. DOI: 10.1016/j.bbr.2013.06.012. View

14.

Fine S, Weissman A, Gerdes M, Pinto-Martin J, Zackai E, McDonald-McGinn D . Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome. J Autism Dev Disord. 2005; 35(4):461-70. PMC: 2814423. DOI: 10.1007/s10803-005-5036-9. View

15.

Ousley O, Evans A, Fernandez-Carriba S, Smearman E, Rockers K, Morrier M . Examining the Overlap between Autism Spectrum Disorder and 22q11.2 Deletion Syndrome. Int J Mol Sci. 2017; 18(5). PMC: 5454981. DOI: 10.3390/ijms18051071. View

16.

Zhang F, Gu W, Hurles M, Lupski J . Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet. 2009; 10:451-81. PMC: 4472309. DOI: 10.1146/annurev.genom.9.081307.164217. View

17.

Chung B, Tao V, Tso W . Copy number variation and autism: new insights and clinical implications. J Formos Med Assoc. 2014; 113(7):400-8. DOI: 10.1016/j.jfma.2013.01.005. View

18.

Hiramoto T, Kang G, Suzuki G, Satoh Y, Kucherlapati R, Watanabe Y . Tbx1: identification of a 22q11.2 gene as a risk factor for autism spectrum disorder in a mouse model. Hum Mol Genet. 2011; 20(24):4775-85. PMC: 3221538. DOI: 10.1093/hmg/ddr404. View

19.

Vicari S, Napoli E, Cordeddu V, Menghini D, Alesi V, Loddo S . Copy number variants in autism spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2019; 92:421-427. DOI: 10.1016/j.pnpbp.2019.02.012. View

20.

Crespi B, Crofts H . Association testing of copy number variants in schizophrenia and autism spectrum disorders. J Neurodev Disord. 2012; 4(1):15. PMC: 3436704. DOI: 10.1186/1866-1955-4-15. View