Türkiye’nin Güneydoğu Anadolu Bölgesindeki Distoni Genetiği

Yıl 2025, Cilt: 22 Sayı: 4

Mehmet Burak Mutlu , Özlem Öz

Öz

Amaç: Distoni, distoninin belirgin bir özellik olduğu hiperkinetik hareket bozukluklarını tanımlamak için kullanılan bir terimdir. Etiyolojiye bağlı olarak distoni, edinilmiş, kalıtsal veya idiyopatik olabilir. Bu yollarda genellikle rol oynayan distoni genleri, izole, kompleks ve kombine distoni genleri olarak sınıflandırılır. Bu çalışmada, 60 hastada distoninin genetik nedenlerini tüm eksom dizileme (WES) ile araştırdık. Elde edilen sonuçların genotip-fenotip korelasyonu yapıldı.
Materyal ve Metod: Çalışmaya, 2021 ile 2025 yılları arasında Harran Üniversitesi Tıp Fakültesi Hastanesi’ne sevk edilen 60 hasta (25 kadın, 35 erkek) dahil edildi. Hastalar distoni semptomlarının varlığına göre seçildi. WES uyguladık ve önerilen kılavuzlara göre varyantları değerlendirdik.
Bulgular: WES analizi, kohortun 17 hastasında (yaklaşık %28) patojenik veya muhtemelen patojenik mutasyonların varlığını ortaya çıkardı. Otuz yedi hasta (yaklaşık %62) klinik önemi belirsiz varyantlar (VUS) sergiledi. 6 hastada (%10) WES, distoni ile ilişkili herhangi bir varyasyon saptamadı.
Sonuç: Bu çalışma, Güneydoğu Anadolu Bölgesi’nde distoninin tanı ve tedavisinde genetik testlerin önemli rolünü vurgulamaktadır. Spesifik genetik varyantların tanımlanması, kişiselleştirilmiş tedavi stratejilerinin uygulanmasını kolaylaştırır ve bu da tedavi sonuçlarını iyileştirme ve yan etkileri azaltma potansiyeline sahiptir.

Anahtar Kelimeler

Distoni , Tüm ekzom dizileme , WES , NGS

Dystonia Genetics in the Southeastern Anatolia Region of Türkiye

Öz

Background: Dystonia is a term used to describe hyperkinetic movement disorders in which dystonia is the prominent feature. Depending on the aetiology, dystonia may be acquired, inherited, or idiopathic. The dystonia genes that are usually involved in these pathways are classified as isolated, complex, and combined dystonia genes. In this study, we investigate the genetic causes of dystonia in 60 patients by whole-exsome sequencing (WES). Genotype-phenotype correlation of the obtained results was performed.
Materials and Methods: Sixty patients (25 females, 35 males) were included in the study who were referred to Harran University Medical Faculty Hospital between 2021 and 2025. Patients were selected based on the presence of symptoms of dystonia. We performed WES and evaluated the variants with recommended guidelines.
Results: WES analysis revealed the presence of pathogenic or likely pathogenic mutations in 17 patients (approximately 28%) of the cohort. 37 patients (approximately 62%) exhibited variants of uncertain clinical significance (VUS). In 6 patients (10%), WES did not reveal any variations associated with dystonia.
Conclusions: This study emphasises the pivotal function of genetic testing in the diagnosis and management of dystonia in the southern-eastern Anatolian region. The identification of specific genetic variants facilitates the implementation of personalised treatment strategies, which has the potential to enhance therapeutic outcomes and reduce adverse effects.

Anahtar Kelimeler

Dystonia , Whole-exome sequencing , WES , NGS

Etik Beyan

This study was approved by the Harran University Clinical Research Ethics Committee (approval no: HRÜ/25.09.55, date: May 12, 2025).

Kaynakça

• 1. Albanese A, Di Giovanni M, Lalli S. Dystonia: diagnosis and management. Eur J Neurol. 2019;26(1):5–17.
• 2. Dressler D, Altenmüller E, Giess R, Krauss JK, Adib Saberi F. The epidemiology of dystonia: the Hannover epidemiology study. J Neurol. 2022;269(12):6483–6493.
• 3. Medina A, Nilles C, Martino D, Pelletier C, Pringsheim T. The Prevalence of Idiopathic or Inherited Isolated Dystonia: A Systematic Review and Meta-Analysis. Mov Disord Clin Pract. 2022;9(7):860–868.
• 4. Thomsen M, Lange LM, Zech M, Lohmann K. Genetics and Pathogenesis of Dystonia. Annu Rev Pathol. 2024;19:99–131.
• 5. Marras C, Lang A, van de Warrenburg BP, Sue CM, Tabrizi SJ, Bertram L, et al. Nomenclature of genetic movement disorders: Recommendations of the international Parkinson and movement disorder society task force. Mov Disord. 2016;31(4):436–457.
• 6. Weissbach A, Saranza G, Domingo A. Combined dystonias: clinical and genetic updates. J Neural Transm (Vienna). 2021;128(4):417–429.
• 7. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–424.
• 8. Zech M, Jech R, Boesch S, Škorvánek M, Weber S, Wagner M, et al. Monogenic variants in dystonia: an exome-wide sequencing study. Lancet Neurol. 2020;19(11):908–918.
• 9. Wirth T, Kumar KR, Zech M. Long-Read Sequencing: The Third Generation of Diagnostic Testing for Dystonia. Mov Disord. 2024.
• 10. Li LX, Liu Y, Huang JH, Yang Y, Pan YG, Zhang XL, et al. Genetic spectrum and clinical features in a cohort of Chinese patients with isolated dystonia. Clin Genet. 2023;103(4):459–465.
• 11. Rexach J, Lee H, Martinez-Agosto JA, Németh AH, Fogel BL. Clinical application of next-generation sequencing to the practice of neurology. Lancet Neurol. 2019;18(5):492–503.
• 12. Eratne D, Schneider A, Lynch E, Martyn M, Velakoulis D, Fahey M, et al. The clinical utility of exome sequencing and extended bioinformatic analyses in adolescents and adults with a broad range of neurological phenotypes: an Australian perspective. J Neurol Sci. 2021;420:117260.
• 13. Bullich G, Matalonga L, Pujadas M, Papakonstantinou A, Piscia D, Tonda R, et al. Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases. J Mol Diagn. 2022;24(5):529–542.
• 14. Alvarez-Mora MI, Rodríguez-Revenga L, Jodar M, Potrony M, Sanchez A, Badenas C, et al. Implementation of Exome Sequencing in Clinical Practice for Neurological Disorders. Genes (Basel). 2023;14(4):813. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137364/
• 15. Gultekin M, Prakash N, Ganos C, Mirza M, Bayramov R, Bhatia KP, et al. A Novel SGCE Nonsense Variant Associated With Marked Intrafamilial Variability in a Turkish Family With Myoclonus-Dystonia. Mov Disord Clin Pract. 2019;6(6):479–482.
• 16. Bonafé L, Thöny B, Penzien JM, Czarnecki B, Blau N. Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia. Am J Hum Genet. 2001;69(2):269–277.
• 17. Liu T, Fan Y, Jiao X, Liu H, Wang S, Chen S, et al. Genetic screening in patients of Meige syndrome and blepharospasm. Brain Behav. 2022;12(2):e2474. Available from: https://pubmed.ncbi.nlm.nih.gov/35044558/