Journal of Istanbul Faculty of Medicine

SUBMITINFORMATION
EnglishTürkçe

Research Article


DOI :10.26650/IUITFD.427250   IUP :10.26650/IUITFD.427250    Full Text (PDF)

CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS

Şahin Avcı, Güven Toksoy, Gülendam Bağırova, Umut Altunoğlu, Birsen Karaman, Seher Başaran, Hülya Kayserili Karabey, Zehra Oya Uyguner

Objective: Radial ray defects (RRDs) are the most common congenital abnormality of the upper extremities, with a prevalence of 1:30,000. 70% of RRDs are syndromic or accompanied by additional malformations, whereas 30% are in isolated form. Definitive diagnosis is critical for follow-up and provides an opportunity for prenatal diagnosis. The aim of this study was to provide a guide for the differential diagnosis of patients with RRD via contributing to their molecular diagnosis by constructing a next-generation sequencing (NGS) gene-panel test. 

Materials and Methods: 48 probands from 37 families, referred for genetic consultation due to RRD, between the years of 2004– 2014, were evaluated by cytogenetic and molecular tools following clinical examinations. 31 probands, with normal karyotype, were screened for 43 RRD associated genes of 14 syndromes by using in-house-designed targeted NGS gene-panel. 

Results: Chromosomal abnormalities [a trisomy 18 and a familial reciprocal translocation t(2;12)(q31;q24.3)] in two families and mutations in related genes (SF3B4, SALL4, TBX5, FANCA) in four families were known before the initiation of this study. In remaining 31 probands, five families identified to have six different mutations in four different genes (FANCA, NIPBL, ESCO2, BRIP1). 

Conclusion: Chromosomal abnormalities in two of the 37 families (5.4%) and gene mutations in nine of the 37 families (24.3%) were identified. Our study demonstrated that an in-house-designed targeted NGS containing 43 genes made considerable contribution to the diagnosis of RRD. Moreover, chromosomal abnormalities must always be considered in the differential diagnosis and excluded before gene-panel screening. 
Keywords: Fanconi anemia, next-generation sequencing, radial ray defects
DOI :10.26650/IUITFD.427250   IUP :10.26650/IUITFD.427250    Full Text (PDF)

RADİYAL IŞIN DEFEKTLERİNİN KLİNİK SINIFLANDIRMASI VE ETYOPATOGENEZİNİN ARAŞTIRILMASI

Şahin Avcı, Güven Toksoy, Gülendam Bağırova, Umut Altunoğlu, Birsen Karaman, Seher Başaran, Hülya Kayserili Karabey, Zehra Oya Uyguner

Amaç: Radiyal ışın defektleri (RID) 1/30.000 prevalansı ile üst ekstremitenin en sık gözlenen konjenital anomalisidir. Olguların yaklaşık %30’unda RID izole olarak, %70’inde ek anomaliler veya sendromlar ile birlikte gözlenir. Bu nedenle, olgularda tanının kesinleşmesi, izlemi, ailelere özgün genetik danışma verilmesi ve sonraki gebeliklerinde prenatal tanı seçeneğinin sunulabilmesi için önemlidir. Bu çalışma ile RID olgularının ayırıcı tanısında yol gösterici olması, moleküler tanıya katkı sağlaması amacıyla yeni nesil dizileme (YND) gen-paneli oluşturuldu ve panelin moleküler tanıdaki etkinliği araştırıldı. 

Gereç ve Yöntem:  Bu çalışmada, 2004-2014 yılları arasında kliniğimizde RID bulgusu ile değerlendirilen 37 aileden 48 etkilenmiş olgunun klinik, moleküler ve sitogenetik bulguları değerlendirildi. Karyotipi normal saptanan ve moleküler tanısı olmayan 31 ailenin indeks olgusunda 14 farklı fenotip ile ilişkili 43 gen, RID için tasarladığımız hedefe yönelik YND paneli ile dizilendi. 

Bulgular: Sitogenetik analiz ile bir olguda trizomi 18 ve diğer bir olguda ise ailevi t(2;12)(q31;q24.3) translokasyonu saptandı. Dört ailede ilişkili genlerdeki (SF3B4, SALL4, TBX5, FANCA) mutasyonlar çalışma öncesinde moleküler analizlerle belirlenmişti. Tanısı olmayan 31 indeks olgunun 5’inde (%16), 4 farklı gende (FANCA, NIPBL, ESCO2, BRIP1) 6 farklı mutasyon saptandı. 

Sonuç: RID nedeniyle değerlendirilen 37 ailenin 2’sinde (%5.4) kromozom anomalisi ve 9’unda (%24.3) 7 farklı gende 9 farklı mutasyon saptandı. Bulgularımız, RID olgularında özgün tasarlanan yeni nesil dizileme panelimizin moleküler tanıya önemli oranda katkı sağladığını; RID’ın etyopatogenezinde kromozom anomalilerinin de yer aldığını, ayırıcı tanıda yer alması ve RID-panel çalışmasından önce kromozom anomalilerinin dışlanması gerektiğini gösterdi. 
Keywords: Fanconi anemisi, radial ışın defektleri, yeni nesil dizileme

PDF View

References

  • 1. Ashhurst DE. The influence of mechanical conditions on the healing of experimental fractures in the rabbit: a microscopical study. Philos Trans R Soc Lond B Biol Sci 1986;313(1161):271 - 302. google scholar
  • 2. Bellaiche N. Imaging in oral implantology. In: Scortecchi GM, Misch CE, Benner KU (eds). Implants and Restorative Dentistry. London, England: Martin Dunitz Ltd, 2001;181. google scholar
  • 3. Bouckenooghe T, Remacle C, Reusens B. Is taurine a functional nutrient? Curr Opin Clin Nutr Metab Care 2006;9(6):728-33. google scholar
  • 4. Buckwalter JA. Musculoskeletal tissue healing. In: Weinstein SL, Buckwalter JA (eds). Turek’s Orthopaedics, Principles and Their Applications, 6th ed. Philadelphia, Pennsylvania, USA: Lippincott Williams & Wilkins, 2005;57-63. google scholar
  • 5. Cetinus E, Kilinc M, Uzel M, et al. Does long-term ischemia affect the oxidant status during fracture healing? Arch Orthop Trauma Surg 2005;125(6):376-80. google scholar
  • 6. Demers LM. Bone specific alkaline phosphatase. In: Eastell R, Baumann M, Hoyle NR, Wieczorek L (eds). Bone Markers Biochemical and Clinical Perspectives, London, England: Martin Dunitz Ltd, 2001;57-8. google scholar
  • 7. Durak K, Sönmez G, Sarisozen B, Özkan S, Kaya M, Öztürk C. Histological assessment of the effect of alpha-tocopherol on fracture healing in rabbits. J Int Med Res 2003;31(1):26-30. google scholar
  • 8. Duygulu F, Yakan B, Karaoğlu S, Kutlubay R, Karahan OI, Özturk A. The effect of zymosan and the protective effect of various antioxidants on fracture healing in rats. Arch Orthop Trauma Surg 2007;127(7):493-501. google scholar
  • 9. Frost HM. The biology of fracture healing. An overview for clinicians. Part I. Clin Orthop Relat Res 1989;248:283-93. google scholar
  • 10. Garrett IR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR. Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest 1990;85(3):632-9. google scholar
  • 11. Göktürk E, Turgut A, Baycu C, Günal I, Seber S, Gülbaş Z. Oxygen free radicals impair fracture healing in rats. Acta Orthop Scand 1995;66(5):473-5. google scholar
  • 12. Goldberg VM, Powell A, Shaffer JW, Zika J, Bos GD, Heiple KG. Bone grafting: role of histocompatibility in transplantation. J Orthop Res 1985;3(4):389-404. google scholar
  • 13. Halıcı M, Öner M, Güney A, Canöz Ö, Narin F, Halıcı C. Melatonin promotes fracture healing in the rat model. Eklem Hastalik Cerrahisi 2010;21(3):172-7. google scholar
  • 14. Huo MH, Troiano NW, Pelker RR, Gundberg CM, Friedlaender GE. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res 1991;9(3):383-90. google scholar
  • 15. Huxtable RJ. Physiological actions of taurine. Physiol Rev 1992;72(1):101-63. google scholar
  • 16. Kim JW, Kim C. Inhibition of LPS-induced NO production by taurine chloramine in macrophages is mediated though Ras-ERK-NF-kappaB. Biochem Pharmacol 2005;70(9):1352-60. google scholar
  • 17. Lykkesfeldt J. Determination of malondialdehyde as dithiobarbituric acid adduct in biological samples by HPLC with fluorescence detection: comparison with ultraviolet-visible spectrophotometry. Clin Chem 2001;47(9):1725-7. google scholar
  • 18. Mohamad S, Shuid AN, Mohamed N, et al. The effects of alpha-tocopherol supplementation on fracture healing in a postmenopausal osteoporotic rat model. Clinics (Sao Paulo) 2012;67(9):1077-85. google scholar
  • 19. Mohamadnia AR, Shahbazkia HR, Sharifi S, Shafaei I. Bone-specificalkaline phosphatase as a good indicator of bone formation in sheepdogs. Comp Clin Pathol 2007;16(4):265-70. google scholar
  • 20. Park E, Alberti J, Quinn MR, Schuller-Levis G. Taurine chloramine inhibits the production of superoxide anion, IL-6 and IL-8 in activated human polymorphonuclear leukocytes. Adv Exp Med Biol 1998;442:177-82. google scholar
  • 21. Park S, Kim H, Kim SJ. Stimulation of ERK2 by taurine with enhanced alkaline phosphatase activity and collagen synthesis in osteoblast-like UMR-106 cells. Biochem Pharmacol 2001;62(8):1107-11. google scholar
  • 22. Petrovich YA, Podorozhnaya RP, Kichenko SM, Kozlova MV. Effects of selenium-containing compounds and their metabolism in intact rats and in animals with bone fractures. Bull Exp Biol Med 2004;137(1):74-7. google scholar
  • 23. Pincemail J. Free radicals and antioxidants in human diseases. In: Favier AE, Cadet J, Kalyanaraman B, Fontecave M, Pierre JL eds. Analysis of free radicals in biological systems, Basel, Switzerland: Birkhäuser; 1995: 83-98. google scholar
  • 24. Roysommuti S, Azuma J, Takahashi K, Schaffer S. Taurine cytoprotection: From cell to system. Thai J Physiol Sci 2003;16(2):17-27. google scholar
  • 25. Rozen N, Lewinson D, Bick T, Meretyk S, Soudry M. Role of bone regeneration and turnover modulators in control of fracture. Crit Rev Eukaryot Gene Expr 2007;17(3):197-213. google scholar
  • 26. Sarisozen B, Durak K, Dincer G, Bilgen OF. The effects of vitamins E and C on fracture healing in rats. J Int Med Res 2002;30(3):309-13. google scholar
  • 27. Schuller-Levis GB, Park E. Taurine and its chloramine: modulators of immunity. Neurochem Res 2004;29(1):117-26. google scholar
  • 28. Shuid AN, Mohamad S, Muhammad N, et al. Effects of α-tocopherol on the early phase of osteoporotic fracture healing. J Orthop Res 2011;29(11):1732-8. google scholar
  • 29. Silverton SF, Mesaros S, Markham GD, Malinski T. Osteoclast radical interactions: NADPH causes pulsatile release of NO and stimulates superoxide production. Endocrinology 1995; 136(11):5244-7. google scholar
  • 30. Sontakke AN, Tare RS. A duality in the roles of reactive oxygen species with respect to bone metabolism. Clin Chim Acta 2002;318(1-2):145-8. google scholar
  • 31. Turgut A, Göktürk E, Köse N, Kaçmaz M, Oztürk HS, Seber S, et al. Oxidant status increased during fracture healing in rats. Acta Orthop Scand 1999;70(5):487-90. google scholar
  • 32. Turk C, Halici M, Guney A, Akgun H, Sahin V, Muhtaroglu S. Promotion of fracture healing by vitamin E in rats. J Int Med Res 2004;32(5):507-12. google scholar
  • 33. Volkmer DL, Sears B, Lauing KL, Nauer RK, Roper PM, Yong S, et al. Antioxidant therapy attenuates deficient bone fracture repair associated with binge alcohol exposure. J Orthop Trauma 2011;25(8):516-21. google scholar
  • 34. Wojtecka-Lukasik E, Czuprynska K, Maslinska D, Gajewski M, Gujski M, Maslinski S. Taurine-chloramine is a potent anti-inflammatory substance. Inflamm Res 2006;55 Suppl 1:S17-S18. google scholar
  • 35. Yeler H, Tahtabas F, Candan F. Investigation of oxidative stress during fracture healing in the rats. Cell Biochem Funct 2005;23(2):137-9. google scholar
  • 36. Yilmaz C, Erdemli E, Selek H, Kinik H, Arikan M, Erdemli B. The contribution of vitamin C to healing of experimental fractures. Arch Orthop Trauma Surg 2001;121(7):426-8. google scholar
  • 37. Yuan LQ, Liu W, Cui RR, Wang D, Meng JC, Xie H, et al. Taurine inhibits osteoclastogenesis through the taurine transporter. Amino Acids 2010;39(1):89-99. google scholar
  • 38. Yuan LQ, Xie H, Luo XH, Wu XP, Zhou HD, Lu Y, et al. Taurine transporter is expressed in osteoblasts. Amino Acids 2006;31(2):157-63. google scholar
  • 39. Zhou C, Zhang X, Xu L, Wu T, Cui L, Xu D. Taurine promotes human mesenchymal stem cells to differentiate into osteoblast through the ERK pathway. Amino Acids 2014;46(7):1673 - 80. google scholar

Citations

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


EXPORT



APA

Avcı, Ş., Toksoy, G., Bağırova, G., Altunoğlu, U., Karaman, B., Başaran, S., Kayserili Karabey, H., & Uyguner, Z.O. (2018). CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS. Journal of Istanbul Faculty of Medicine, 81(4), 127-138. https://doi.org/10.26650/IUITFD.427250


AMA

Avcı Ş, Toksoy G, Bağırova G, Altunoğlu U, Karaman B, Başaran S, Kayserili Karabey H, Uyguner Z O. CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS. Journal of Istanbul Faculty of Medicine. 2018;81(4):127-138. https://doi.org/10.26650/IUITFD.427250


ABNT

Avcı, Ş.; Toksoy, G.; Bağırova, G.; Altunoğlu, U.; Karaman, B.; Başaran, S.; Kayserili Karabey, H.; Uyguner, Z.O. CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS. Journal of Istanbul Faculty of Medicine, [Publisher Location], v. 81, n. 4, p. 127-138, 2018.


Chicago: Author-Date Style

Avcı, Şahin, and Güven Toksoy and Gülendam Bağırova and Umut Altunoğlu and Birsen Karaman and Seher Başaran and Hülya Kayserili Karabey and Zehra Oya Uyguner. 2018. “CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS.” Journal of Istanbul Faculty of Medicine 81, no. 4: 127-138. https://doi.org/10.26650/IUITFD.427250


Chicago: Humanities Style

Avcı, Şahin, and Güven Toksoy and Gülendam Bağırova and Umut Altunoğlu and Birsen Karaman and Seher Başaran and Hülya Kayserili Karabey and Zehra Oya Uyguner. “CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS.” Journal of Istanbul Faculty of Medicine 81, no. 4 (May. 2025): 127-138. https://doi.org/10.26650/IUITFD.427250


Harvard: Australian Style

Avcı, Ş & Toksoy, G & Bağırova, G & Altunoğlu, U & Karaman, B & Başaran, S & Kayserili Karabey, H & Uyguner, ZO 2018, 'CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS', Journal of Istanbul Faculty of Medicine, vol. 81, no. 4, pp. 127-138, viewed 29 May. 2025, https://doi.org/10.26650/IUITFD.427250


Harvard: Author-Date Style

Avcı, Ş. and Toksoy, G. and Bağırova, G. and Altunoğlu, U. and Karaman, B. and Başaran, S. and Kayserili Karabey, H. and Uyguner, Z.O. (2018) ‘CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS’, Journal of Istanbul Faculty of Medicine, 81(4), pp. 127-138. https://doi.org/10.26650/IUITFD.427250 (29 May. 2025).


MLA

Avcı, Şahin, and Güven Toksoy and Gülendam Bağırova and Umut Altunoğlu and Birsen Karaman and Seher Başaran and Hülya Kayserili Karabey and Zehra Oya Uyguner. “CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS.” Journal of Istanbul Faculty of Medicine, vol. 81, no. 4, 2018, pp. 127-138. [Database Container], https://doi.org/10.26650/IUITFD.427250


Vancouver

Avcı Ş, Toksoy G, Bağırova G, Altunoğlu U, Karaman B, Başaran S, Kayserili Karabey H, Uyguner ZO. CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS. Journal of Istanbul Faculty of Medicine [Internet]. 29 May. 2025 [cited 29 May. 2025];81(4):127-138. Available from: https://doi.org/10.26650/IUITFD.427250 doi: 10.26650/IUITFD.427250


ISNAD

Avcı, Şahin - Toksoy, Güven - Bağırova, Gülendam - Altunoğlu, Umut - Karaman, Birsen - Başaran, Seher - Kayserili Karabey, Hülya - Uyguner, ZehraOya. “CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS”. Journal of Istanbul Faculty of Medicine 81/4 (May. 2025): 127-138. https://doi.org/10.26650/IUITFD.427250



TIMELINE


Submitted25.05.2018
Accepted05.11.2018
Published Online01.12.2018

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.