Research Article


DOI :10.26650/experimed.1380210   IUP :10.26650/experimed.1380210    Full Text (PDF)

Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability

Deniz Sünnetçi AkkoyunluBülent KaraNaci CineSeda Eren KeskinBuket DoğruoğluZeynep İlkayTolgahan ÖzerHakan Savlı

Objective: Intellectual disability (ID) is a complex, variable, and clinically heterogeneous neurodevelopmental disorder that affects 1% – 3% of the global population. Copy number variations (CNVs) contribute to approximately 15%–20% of ID cases. Array comparative genomic hybridization (aCGH) is the first-line test for diagnosing patients with ID with/without multiple congenital anomalies (MCAs). This study aimed to present CNVs identified in a retrospective aCGH cohort of Turkish patients with ID with/without other medical conditions.

Materials and Methods: The study population consisted of 210 patients (139 male, 71 female) aged 2–18 years. aCGH analysis was performed using oligo and bacterial artificial chromosome (BAC)-based microarray platforms. CNVs were interpreted using public databases and literature mining and categorized according to international guidelines.

Results: Forty-five CNVs were detected in 38 (18%) patients. Among these CNVs, 21 (46.6%) were pathogenic, 4 (8.8%) were likely pathogenic, and 8 (17.7%) were variants of uncertain clinical significance (VUS). Nineteen CNVs corresponded to rare microdeletion/ microduplication syndromes.

Conclusions: This study reports rare CNVs or syndromes among Turkish patients with ID with/without other medical conditions. Data revealed an overall diagnostic rate of 11.43%, which confirms aCGH as the first-line technology allowing geneticists to diagnose complex phenotypes, identify candidate genes involved in ID, and explore novel CNV effects.


PDF View

References

  • 1. Pereira RR, Pinto IP, Minasi LB, de Melo AV, da Cruz e Cunha DM, Cruz AS, et al. Screening for intellectual disability using high-resolution CMA technology in a retrospective cohort from Central Brazil. PLoS One 2014; 9: e103117. google scholar
  • 2. Quintela I, Eirfs J, Gömez-Lado C, Perez-Gay L, Dacruz D, Cruz R, et al. Copy number variation analysis of patients with intellectual disability from North-West Spain. Gene 2017; 626: 189-99. google scholar
  • 3. Vianna GS, Medeiros PF, Alves AF, Silva TO, Jehee FS. Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil. Genet Mol Res 2016; 15. google scholar
  • 4. Wolfe K, Strydom A, Morrogh D, Carter J, Cutajar P, Eyeoyibo M, et al. Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders. Eur J Hum Genet 2016; 25: 66-72. google scholar
  • 5. Di Gregorio E, Riberi E, Belligni EF, Biamino E, Spielmann M, Ala U, et al. Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes. Clin Genet 2017; 92: 415-22. google scholar
  • 6. Lee CL, Lee CH, Chuang CK, Chiu HC, Chen YJ, Chou CL, et al. Array-CGH increased the diagnostic rate of developmental delay or intellectual disability in Taiwan. Pediatr Neonatol 2019; 60: 453-60. google scholar
  • 7. Moorhead PS, Nowell PC, Mellman WJ, Battıps DM, Hungerford DA. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res 1960; 20: 613-6. google scholar
  • 8. Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST, Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med 2011; 13: 680-5. google scholar
  • 9. Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 2020; 22: 245-57. google scholar
  • 10. Türkyılmaz A, Geckinli BB, Tekin E, Ates EA, Yarali O, Cebi AH, et al. Array-based comparative genomic hybridization analysis in children with developmental delay/intellectual disability. Balkan J Med Genet 2022; 24: 15-24. google scholar
  • 11. Chen CP, Wang LK, Chern SR, Wu PS, Chen SW, Wu FT, et al. Prenatal diagnosis and molecular cytogenetic characterization of mosaic ring chromosome 21 associated with low PAPP-A and low PlGF in the first-trimester maternal serum screening. Taiwan J Obstet Gynecol 2022; 61: 359-63. google scholar
  • 12. Conti V, Carabalona A, Pallesi-Pocachard E, Parrini E, Leventer RJ, Buhler E, et al. Periventricular heterotopia in 6q terminal deletion syndrome: role of the C6orf70 gene. Brain 2013; 136: 3378-94. google scholar
  • 13. Jang W, Chae H, Kim J, Son JO, Kim SC, Koo BK, et al. Identification of small marker chromosomes using microarray comparative genomic hybridization and multicolor fluorescent in situ hybridization. Mol Cytogenet 2016; 9: 61. google scholar
  • 14. Sifakis S, Eleftheriades M, Kappou D, Murru R, Konstantinidou A, Orru S, et al. Prenatal diagnosis of proximal partial trisomy 1q confirmed by comparative genomic hybridization array: molecular cytogenetic analysis, fetal pathology and review of the literature. Birth Defects Res A Clin Mol Teratol 2014; 100: 284-93. google scholar
  • 15. Quintela I, Barros F, Fernandez-Prieto M, Martinez-Regueiro R, Castro-Gago M, Carracedo A, et al. Interstitial microdeletions including the chromosome band 4q13.2 and the UBA6 gene as possible causes of intellectual disability and behavior disorder. Am J Med Genet A 2015; 167A: 3113-20. google scholar
  • 16. Kirchhoff M, Bisgaard AM, Stoeva R, Dimitrov B, Gillessen-Kaesbach G, Fryns JP, et al. Phenotype and 244k array-CGH characterization of chromosome 13q deletions: an update of the phenotypic map of 13q21.1-qter. Am J Med Genet A 2009; 149A: 894-905. google scholar
  • 17. Lennon PA, Boerkoel CF, Plunkett K, Soukam S, Cheung SW, Patel A. A novel 8.5 MB dup(1)(p34.1p34.3) characterized by FISH in a child presenting with congenital heart defect and dysmorphic features. Am J Med Genet A 2006; 140A: 1864-70. google scholar
  • 18. Jacher JE, Innis JW. Interstitial microdeletion of the 1p34.3p34.2 region. Mol Genet Genomic Med 2018; 6: 673-7. google scholar
  • 19. Rosenfeld JA, Patel A. Chromosomal microarrays: understanding genetics of neurodevelopmental disorders and congenital anomalies. J Pediatr Genet. 2017; 6: 42-50. google scholar
  • 20. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010; 86: 749-64. google scholar
  • 21. Hochstenbach R, van Binsbergen E, Engelen J, Nieuwint A, Polstra A, Poddighe P, et al. Array analysis and karyotyping: workflow consequences based on a retrospective study of 36,325 patients with idiopathic developmental delay in the Netherlands. Eur J Med Genet 2009; 52: 161-9. google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Sünnetçi Akkoyunlu, D., Kara, B., Cine, N., Keskin, S.E., Doğruoğlu, B., İlkay, Z., Özer, T., & Savlı, H. (2023). Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability. Experimed, 13(3), 263-275. https://doi.org/10.26650/experimed.1380210


AMA

Sünnetçi Akkoyunlu D, Kara B, Cine N, Keskin S E, Doğruoğlu B, İlkay Z, Özer T, Savlı H. Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability. Experimed. 2023;13(3):263-275. https://doi.org/10.26650/experimed.1380210


ABNT

Sünnetçi Akkoyunlu, D.; Kara, B.; Cine, N.; Keskin, S.E.; Doğruoğlu, B.; İlkay, Z.; Özer, T.; Savlı, H. Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability. Experimed, [Publisher Location], v. 13, n. 3, p. 263-275, 2023.


Chicago: Author-Date Style

Sünnetçi Akkoyunlu, Deniz, and Bülent Kara and Naci Cine and Seda Eren Keskin and Buket Doğruoğlu and Zeynep İlkay and Tolgahan Özer and Hakan Savlı. 2023. “Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability.” Experimed 13, no. 3: 263-275. https://doi.org/10.26650/experimed.1380210


Chicago: Humanities Style

Sünnetçi Akkoyunlu, Deniz, and Bülent Kara and Naci Cine and Seda Eren Keskin and Buket Doğruoğlu and Zeynep İlkay and Tolgahan Özer and Hakan Savlı. Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability.” Experimed 13, no. 3 (Jul. 2024): 263-275. https://doi.org/10.26650/experimed.1380210


Harvard: Australian Style

Sünnetçi Akkoyunlu, D & Kara, B & Cine, N & Keskin, SE & Doğruoğlu, B & İlkay, Z & Özer, T & Savlı, H 2023, 'Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability', Experimed, vol. 13, no. 3, pp. 263-275, viewed 17 Jul. 2024, https://doi.org/10.26650/experimed.1380210


Harvard: Author-Date Style

Sünnetçi Akkoyunlu, D. and Kara, B. and Cine, N. and Keskin, S.E. and Doğruoğlu, B. and İlkay, Z. and Özer, T. and Savlı, H. (2023) ‘Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability’, Experimed, 13(3), pp. 263-275. https://doi.org/10.26650/experimed.1380210 (17 Jul. 2024).


MLA

Sünnetçi Akkoyunlu, Deniz, and Bülent Kara and Naci Cine and Seda Eren Keskin and Buket Doğruoğlu and Zeynep İlkay and Tolgahan Özer and Hakan Savlı. Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability.” Experimed, vol. 13, no. 3, 2023, pp. 263-275. [Database Container], https://doi.org/10.26650/experimed.1380210


Vancouver

Sünnetçi Akkoyunlu D, Kara B, Cine N, Keskin SE, Doğruoğlu B, İlkay Z, Özer T, Savlı H. Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability. Experimed [Internet]. 17 Jul. 2024 [cited 17 Jul. 2024];13(3):263-275. Available from: https://doi.org/10.26650/experimed.1380210 doi: 10.26650/experimed.1380210


ISNAD

Sünnetçi Akkoyunlu, Deniz - Kara, Bülent - Cine, Naci - Keskin, SedaEren - Doğruoğlu, Buket - İlkay, Zeynep - Özer, Tolgahan - Savlı, Hakan. Copy Number Variations in a Turkish Cohort of Children with Intellectual Disability”. Experimed 13/3 (Jul. 2024): 263-275. https://doi.org/10.26650/experimed.1380210



TIMELINE


Submitted24.10.2023
Accepted27.11.2023
Published Online28.12.2023

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.