Journal of Istanbul Faculty of Medicine

SUBMITINFORMATION
EnglishTürkçe

Research Article


DOI :10.26650/IUITFD.1636301   IUP :10.26650/IUITFD.1636301    Full Text (PDF)

OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR

İrem Kalay, Çağrı Doğan, Lamia Aliyeva Cavit, Abdullatif Bakir, Buğra Nihat Ağaoğlu

Amaç: Fragile X sendromu (FXS), gecikmiş dil gelişimi, dismorfik özellikler ve zihinsel gelişimin bozulması ile karakterize karmaşık bir nörogelişimsel durumdur. FMR1 genindeki CGG tekrar genişlemesi sonucu ortaya çıkan FXS, otizmin en sık belirlenen genetik nedenidir. FXS’ nin doğru tanısı, etkili yönetim ve tedavi için büyük önem taşımaktadır. Bu çalışma, otizmli bireylerde FXS prevalansını değerlendirmeyi amaçlamaktadır.

Gereç ve Yöntemler: Bu çalışmada 50 hasta üzerinde yapılan fragman analizi ile FMR1 genindeki CGG tekrar uzunlukları değerlendirildi. Elde edilen sonuçlar, tekrarlayan bölgelerin American College of Medical Genetics and Genomics (ACMG), Clinical Mole cular Genetics Society (CMGS) ve European Society of Human Genetics (ESHG) kılavuzlarına uygun olarak sınıflandırılmasıyla yorumlandı.

Bulgular: Literatürde yer alan destekleyici çalışmalar da FXS ile otizm arasındaki bağlantıyı vurgulamaktadır. Çalışma kohortunda üç bireyde (%6) FXS tespit edilmiştir. Bu bulgu, otizm spektrum bozukluğu popülasyonlarında %2 ile %8 arasında değişen prevalans oranlarını bildiren önceki çalışmalarla uyumlu olup, elde edilen sonuçların önemini doğrulamaktadır.

Sonuç: FXS ile idiopatik otizmin örtüşen semptomları tanısal zorluklar yaratmakta olup, hedefe yönelik tedavilerin uygulanabilmesi için FXS’ nin belirlenmesi büyük önem taşımaktadır. Aile öyküsü, risk altındaki bireylerin tanımlanmasında kritik bir rol oynamaktadır. FXS, aile bireylerinde ataksi ve erken menopoz gibi farklı klinik belirtilere yol açabilmektedir. Otizmin genetik etiyolojisinin belirlenmesinde altın standart tekniklerden FMR1 fragman analizi ile FXS ekartasyonu sonrası kapsamlı genetik paneller, otizmin ek nedenlerinin belirlenmesine katkı sağlamaktadır. Bu çalışma, otizm bağlamında FXS için genetik testlerin önemini vurgulamakta, müdahaleleri iyileştirmeyi ve etkilenen ailelere doğru tekrar risk danışmanlığı sağlamayı hedeflemektedir.

Keywords: Fragile X sendromu, otizm spektrum bozukluğu, FMR1 geni, fragman analizi
DOI :10.26650/IUITFD.1636301   IUP :10.26650/IUITFD.1636301    Full Text (PDF)

THE PREVALENCE OF FRAGILE X SYNDROME IN INDIVIDUALS WITH AUTISM SPECTRUM DISORDER: GENETIC INSIGHTS AND DIAGNOSTIC CHALLENGES

İrem Kalay, Çağrı Doğan, Lamia Aliyeva Cavit, Abdullatif Bakir, Buğra Nihat Ağaoğlu

Objective: Fragile X Syndrome (FXS) is a complex neurodevel opmental condition characterised by delayed language develop ment, dysmorphic features, and impaired cognitive development. FXS, which results from CGG repeat expansion in the FMR1 gene, is the most commonly identified genetic cause of autism. Accu rate diagnosis of FXS is crucial for effective management and treatment. This study aimed to evaluate the prevalence of FXS in individuals with Autism Spectrum Disorder (ASD).

Material and Methods: We conducted a retrospective study involv ing 50 patients. Comprehensive fragment analysis of the FMR1 gene was performed, with repeat sequences classified according to the stringent guidelines established by American College of Medical Genetics and Genomics (ACMG), Clinical Molecular Genetics Society (CMGS) ve European Society of Human Genetics (ESHG).

Results: FXS was identified in three individuals (6%) within the study cohort. This finding aligns with previous reports indicating prevalence rates between 2% and 8% among ASD populations, thereby confirming the significance of our results.

Conclusion: The overlapping symptoms of FXS and idiopathic autism present diagnostic challenges, highlighting the importance of identifying FXS to implement targeted therapies. Family history is critical in identifying at risk individuals, as FXS can lead to varied manifestations in family members, including ataxia and  early menopause. Although this study provides valuable insights, the limited sample size underscores the need for larger scale research. Advanced genetic investigations and comprehensive panels could further aid in identifying additional causes of autism. This study emphasises the significance of genetic testing for FXS in the context of autism, aiming to enhance interventions and provide accurate recurrence risk counseling for families affected by this prevalent condition.

Keywords: Fragile X Syndrome, autism spectrum disorder, FMR1 gene, fragment analysis

PDF View

References

  • Harris SW, Hessl D, Goodlin-Jones B, Ferranti J, Bacalman S, Barbato I, et al. Autism profiles of males with fragile X syndrome. In: MacLean WE Jr, Abbeduto L, editors. Am J Ment Retard2008;113(6):427-38. google scholar
  • Hnoonual A, Plong-On O, Worachotekamjorn J, Charalsawadi C, Limprasert P. Clinical and molecular characteristics of FMR1 microdeletion in patient with fragile X syndrome and review of the literature. Clin Chim Acta 2024;553:117728. google scholar
  • Hunter J, Rivero-Arias O, Angelov A, Kim E, Fotheringham I, Leal J. Epidemiology of fragile X syndrome: A systematic review and meta-analysis. Am J Med Genet A 2014;164(7):1648-58. google scholar
  • Hagerman R. Consideration of connective tissue dysfunction in the AleX syndrome. Am J Med Genet 1984;17(1):111-21. google scholar
  • Chatterji S, Pachter L. Reference based annotation with GeneMapper. Genome Biol 2006;7(4):R29. google scholar
  • Schaefer GB, Mendelsohn NJ. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013;15(5):399-407. google scholar
  • Hunter JE, Berry-Kravis E, Hipp H, Todd PK. FMR1 disorders. In: Adam MP, Feldman J, Mirzaa GM, et al. GeneReviews® Seattle (WA): University of Washington, Seattle; 1993-2025 [updated 2024 May 16; cited 2025]. https://www.ncbi.nlm.nih. gov/books/NBK1384/ google scholar
  • Tassone F, Beilina A, Carosi C, Albertosi S, Bagni C, Li L, et al. Elevated FMR1 mRNA in premutation carriers is due to increased transcription. RNA. 2007;13(4):555-62. google scholar
  • Marlborough M, Welham A, Jones C, Reckless S, Moss J. Autism spectrum disorder in females with fragile X syndrome: a systematic review and meta-analysis of prevalence. J Neurodev Disord2021;13(1):28. google scholar
  • Nolin SL, Brown WT, Glicksman A, Houck GE Jr, Gargano AD, Sullivan A, et al. Expansion of the Fragile X CGG repeat in females with premutation or intermediate alleles. Am J Hum Genet2003;72(2):454-64. google scholar
  • Bailey DB Jr, Hatton DD, Mesibov G, Ament N, Skinner M. Early development, temperament, and functional impairment in autism and fragile X syndrome. J Autism Dev Disord 2000;30(1):49-59. google scholar
  • Rogers SJ, Hepburn SL, Stackhouse T, Wehner E. The behavioral phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. J Dev Behav Pediatr 2001;22(6):409-17. google scholar
  • Hessl D, Dyer-Friedman J, Glaser B, Wisbeck J, Barajas R, Taylor A, et al. The influence of environmental and genetic factors on behavior problems and autistic symptoms in boys and girls with fragile X syndrome. Pediatrics 2001;108(5):E88. google scholar
  • Granata P, Zito A, Cocciadiferro D, Novelli A, Pessina C, Mazza T, et al. Unveiling genetic insights: Array-CGH and WES discoveries in a cohort of 122 children with essential autism spectrum disorder. BMC Genomics 2024;25(1):1186. google scholar

Citations

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


EXPORT



APA

Kalay, İ., Doğan, Ç., Aliyeva Cavit, L., Bakir, A., & Ağaoğlu, B.N. (2025). OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR. Journal of Istanbul Faculty of Medicine, 88(3), 236-242. https://doi.org/10.26650/IUITFD.1636301


AMA

Kalay İ, Doğan Ç, Aliyeva Cavit L, Bakir A, Ağaoğlu B N. OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR. Journal of Istanbul Faculty of Medicine. 2025;88(3):236-242. https://doi.org/10.26650/IUITFD.1636301


ABNT

Kalay, İ.; Doğan, Ç.; Aliyeva Cavit, L.; Bakir, A.; Ağaoğlu, B.N. OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR. Journal of Istanbul Faculty of Medicine, [Publisher Location], v. 88, n. 3, p. 236-242, 2025.


Chicago: Author-Date Style

Kalay, İrem, and Çağrı Doğan and Lamia Aliyeva Cavit and Abdullatif Bakir and Buğra Nihat Ağaoğlu. 2025. “OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR.” Journal of Istanbul Faculty of Medicine 88, no. 3: 236-242. https://doi.org/10.26650/IUITFD.1636301


Chicago: Humanities Style

Kalay, İrem, and Çağrı Doğan and Lamia Aliyeva Cavit and Abdullatif Bakir and Buğra Nihat Ağaoğlu. “OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR.” Journal of Istanbul Faculty of Medicine 88, no. 3 (Sep. 2025): 236-242. https://doi.org/10.26650/IUITFD.1636301


Harvard: Australian Style

Kalay, İ & Doğan, Ç & Aliyeva Cavit, L & Bakir, A & Ağaoğlu, BN 2025, 'OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR', Journal of Istanbul Faculty of Medicine, vol. 88, no. 3, pp. 236-242, viewed 6 Sep. 2025, https://doi.org/10.26650/IUITFD.1636301


Harvard: Author-Date Style

Kalay, İ. and Doğan, Ç. and Aliyeva Cavit, L. and Bakir, A. and Ağaoğlu, B.N. (2025) ‘OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR’, Journal of Istanbul Faculty of Medicine, 88(3), pp. 236-242. https://doi.org/10.26650/IUITFD.1636301 (6 Sep. 2025).


MLA

Kalay, İrem, and Çağrı Doğan and Lamia Aliyeva Cavit and Abdullatif Bakir and Buğra Nihat Ağaoğlu. “OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR.” Journal of Istanbul Faculty of Medicine, vol. 88, no. 3, 2025, pp. 236-242. [Database Container], https://doi.org/10.26650/IUITFD.1636301


Vancouver

Kalay İ, Doğan Ç, Aliyeva Cavit L, Bakir A, Ağaoğlu BN. OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR. Journal of Istanbul Faculty of Medicine [Internet]. 6 Sep. 2025 [cited 6 Sep. 2025];88(3):236-242. Available from: https://doi.org/10.26650/IUITFD.1636301 doi: 10.26650/IUITFD.1636301


ISNAD

Kalay, İrem - Doğan, Çağrı - Aliyeva Cavit, Lamia - Bakir, Abdullatif - Ağaoğlu, BuğraNihat. “OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR”. Journal of Istanbul Faculty of Medicine 88/3 (Sep. 2025): 236-242. https://doi.org/10.26650/IUITFD.1636301



TIMELINE


Submitted17.02.2025
Accepted29.05.2025
Published Online25.06.2025

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.