Analysis of Cytogenetic Abnormalities in Iranian Patients with Syndromic Autism Spectrum Disorder: A Case Series
Iranian Journal of Child Neurology,
Vol. 16 No. 2 (2022),
14 March 2022
,
Page 117-128
https://doi.org/10.22037/ijcn.v16i4.34843
Abstract
Objective
Autism spectrum disorder is a heterogeneous neuropsychiatric group of pervasive development disorder, which is mostly diagnosed through the intricate behavioral phenotype. According to strong genetic involvement, detecting the chromosome regions and the key genes linked to autism can help to elucidate its etiology. The present study aims to investigate the value of cytogenetic analysis in syndromic autism as well as to find an association between autism and chromosome abnormalities.
Materials & Methods
Thirty-six autism patients from 30 families, diagnosed clinically with DSM-5 criteria, were recruited. The syndromic patients who had additional clinical features involving development delay, attention deficit, hyperactivity disorder, seizure, language, and intellectual impairment were selected due to elevating the detection rate. Cytogenetics analysis was performed using GTG banding on the patients' cultured fibroblasts. Moreover, array-comparative genomic hybridization was also performed for a patient with a de novo and novel variant.
Results
Karyotype analysis in 36 syndromic autism patients detected chromosomal abnormalities in two (5.6%) families, including 46,XY,dup(15)(q11.1q11.2) and 46,XX,ins(7)(q11.1q21.3)dn. In the latter, array-comparative genomic hybridization detected three abnormalities on chromosome 7, including deletion and insertion on both arms; 46,XX,del(7)(q21.11q21.3),dup(7)(p11.2p14.1p12.3)dn.
Conclusion
We reported a novel and de novo cytogenetic abnormality on chromosome 7 in an Iranian patient diagnosed with syndromic autism. However, the detection rate in syndromic autism was low which implies that it cannot be utilized as the only diagnostic procedure.
- Autism Spectrum Disorder
- Syndromic
- Karyotype
- array-comparative genomic hybridization
How to Cite
References
2. Association AP. Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub; 2013.
3. Devlin B, Scherer SW. Genetic architecture in autism spectrum disorder. Current opinion in genetics & development. 2012;22(3):229-37.
4. Tick B, Bolton P, Happé F, Rutter M, Rijsdijk F. Heritability of autism spectrum disorders: a meta‐analysis of twin studies. Journal of Child Psychology and Psychiatry. 2016;57(5):585-95.
5. Niu M, Han Y, Dy ABC, Du J, Jin H, Qin J, et al. Autism symptoms in fragile X syndrome. Journal of child neurology. 2017;32(10):903-9.
6. Sundberg M, Sahin M. Cerebellar development and autism spectrum disorder in tuberous sclerosis complex. Journal of child neurology. 2015;30(14):1954-62.
7. Fernandez BA, Scherer SW. Syndromic autism spectrum disorders: moving from a clinically defined to a molecularly defined approach. Dialogues in clinical neuroscience. 2017;19(4):353.
8. Chung BH-Y, Tao VQ, Tso WW-YJJotFMA. Copy number variation and autism: new insights and clinical implications. 2014;113(7):400-8.
9. Shao L, Shaw CA, Lu XY, Sahoo T, Bacino CA, Lalani SR, et al. Identification of chromosome abnormalities in subtelomeric regions by microarray analysis: a study of 5,380 cases. 2008;146(17):2242-51.
10. Bergbaum A, Ogilvie CM. Autism and chromosome abnormalities—A review. Clinical Anatomy. 2016;29(5):620-7.
11. Jäger P, Kuhn-Schlage C. A simple method for high resolution banding of chromosomes in amniotic fluid cells. Human genetics. 1984;65(3):273-7.
12. Bundey S, Hardy C, Vickers S, Kilpatrick M, Corbett J. Duplication of the 15q11‐13 region in a patient with autism, epilepsy and ataxia. Developmental Medicine & Child Neurology. 1994;36(8):736-42.
13. Burnside RD, Pasion R, Mikhail FM, Carroll AJ, Robin NH, Youngs EL, et al. Microdeletion/microduplication of proximal 15q11. 2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay. Human genetics. 2011;130(4):517-28.
14. Clayton-Smith J, Webb T, Cheng X, Pembrey M, Malcolm S. Duplication of chromosome 15 in the region 15q11-13 in a patient with developmental delay and ataxia with similarities to Angelman syndrome. Journal of medical genetics. 1993;30(6):529-31.
15. Baker P, Piven J, Schwartz S, Patil S. Brief report: duplication of chromosome 15q11-13 in two individuals with autistic disorder. Journal of autism and developmental disorders. 1994;24(4):529-35.
16. Filipek PA, Juranek J, Smith M, Mays LZ, Ramos ER, Bocian M, et al. Mitochondrial dysfunction in autistic patients with 15q inverted duplication. Annals of neurology. 2003;53(6):801-4.
17. Thomas J, Johnson J, Peterson Kraai T, Wilson R, Tartaglia N, LeRoux J, et al. Genetic and clinical characterization of patients with an interstitial duplication 15q11‐q13, emphasizing behavioral phenotype and response to treatment. American Journal of Medical Genetics Part A. 2003;119(2):111-20.
18. Orrico A, Zollino M, Galli L, Buoni S, Marangi G, Sorrentino V. Late‐onset Lennox–Gastaut syndrome in a patient with 15q11. 2–q13. 1 duplication. American Journal of Medical Genetics Part A. 2009;149(5):1033-5.
19. Domínguez-Iturza N, Lo AC, Shah D, Armendáriz M, Vannelli A, Mercaldo V, et al. The autism-and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour. Nature communications. 2019;10(1):1-13.
20. Firouzabadi SG, Vameghi R, Kariminejad R, Darvish H, Banihashemi S, Moghaddam MF, et al. Analysis of copy number variations in patients with autism using cytogenetic and MLPA techniques: report of 16p13. 1p13. 3 and 10q26. 3 duplications. 2016;5(4):236.
- Abstract Viewed: 459 times