Yıl: 2021 Cilt: 51 Sayı: 2 Sayfa Aralığı: 490 - 500 Metin Dili: İngilizce DOI: 10.3906/sag-2003-259 İndeks Tarihi: 21-01-2022

Identification of novel TUBB1 variants in patients with macrothrombocytopenia

Öz:
Background/aim: Macrothrombocytopenia is an autosomal-dominant disorder characterized by increased platelet size and a decreased number of circulating platelets. The membrane skeleton and the link between actin filaments of the skeleton and microtubules, which consist of alpha and beta tubulin [including the tubulin beta-1 chain (TUBB1)] heterodimers, are important for normal platelet morphology, and defects in these systems are associated with macrothrombocytopenia. Materials and methods: In this study, we sequenced the exons of the TUBB1 gene using DNA isolated from the peripheral blood samples of healthy controls (n = 47) and patients with macrothrombocytopenia (n = 37) from Turkey. The TUBB1 expression levels in fractioned blood samples from patients and healthy controls were analyzed by RT-qPCR and Western blot. Microtubule organization of the platelets in the peripheral blood smears of patients, and in mutant TUBB1-transfected HeLa cells, were analyzed by immunofluorescence staining. Results: A new TUBB1 c.803G>T (p.T178T) variant was detected in all of the control and patient samples. Importantly, we found 3 new heterozygous TUBB1 variants predicting amino acid substitutions: G146R (in 1 patient), E123Q (in 1 patient), and T274M (in 4 patients); the latter variant was associated with milder thrombocytopenia in cancer patients treated with paclitaxel. Ectopic expression of TUBB1 T274M/R307H variant in HeLa cells resulted in irregular microtubule organization. Conclusion: Further clinical and functional studies of the newly identified TUBB1 variants may offer important insights into their pathogenicity in macrothrombocytopenia.Key words: TUBB1, macrothrombocytopenia, MYH9, platelets
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APA ÇALIŞKANER Z, Abdul Waheed A, TUZLAKOGLU OZTURK M, Oymak Y, TAZEBAY U, akar n, Kandilci A, Ozkan D (2021). Identification of novel TUBB1 variants in patients with macrothrombocytopenia. , 490 - 500. 10.3906/sag-2003-259
Chicago ÇALIŞKANER Zihni Onur,Abdul Waheed Abdullah,TUZLAKOGLU OZTURK MERVE,Oymak Yeşim,TAZEBAY UYGAR HALIS,akar nejat,Kandilci Ayten,Ozkan Didem Identification of novel TUBB1 variants in patients with macrothrombocytopenia. (2021): 490 - 500. 10.3906/sag-2003-259
MLA ÇALIŞKANER Zihni Onur,Abdul Waheed Abdullah,TUZLAKOGLU OZTURK MERVE,Oymak Yeşim,TAZEBAY UYGAR HALIS,akar nejat,Kandilci Ayten,Ozkan Didem Identification of novel TUBB1 variants in patients with macrothrombocytopenia. , 2021, ss.490 - 500. 10.3906/sag-2003-259
AMA ÇALIŞKANER Z,Abdul Waheed A,TUZLAKOGLU OZTURK M,Oymak Y,TAZEBAY U,akar n,Kandilci A,Ozkan D Identification of novel TUBB1 variants in patients with macrothrombocytopenia. . 2021; 490 - 500. 10.3906/sag-2003-259
Vancouver ÇALIŞKANER Z,Abdul Waheed A,TUZLAKOGLU OZTURK M,Oymak Y,TAZEBAY U,akar n,Kandilci A,Ozkan D Identification of novel TUBB1 variants in patients with macrothrombocytopenia. . 2021; 490 - 500. 10.3906/sag-2003-259
IEEE ÇALIŞKANER Z,Abdul Waheed A,TUZLAKOGLU OZTURK M,Oymak Y,TAZEBAY U,akar n,Kandilci A,Ozkan D "Identification of novel TUBB1 variants in patients with macrothrombocytopenia." , ss.490 - 500, 2021. 10.3906/sag-2003-259
ISNAD ÇALIŞKANER, Zihni Onur vd. "Identification of novel TUBB1 variants in patients with macrothrombocytopenia". (2021), 490-500. https://doi.org/10.3906/sag-2003-259
APA ÇALIŞKANER Z, Abdul Waheed A, TUZLAKOGLU OZTURK M, Oymak Y, TAZEBAY U, akar n, Kandilci A, Ozkan D (2021). Identification of novel TUBB1 variants in patients with macrothrombocytopenia. Turkish Journal of Medical Sciences, 51(2), 490 - 500. 10.3906/sag-2003-259
Chicago ÇALIŞKANER Zihni Onur,Abdul Waheed Abdullah,TUZLAKOGLU OZTURK MERVE,Oymak Yeşim,TAZEBAY UYGAR HALIS,akar nejat,Kandilci Ayten,Ozkan Didem Identification of novel TUBB1 variants in patients with macrothrombocytopenia. Turkish Journal of Medical Sciences 51, no.2 (2021): 490 - 500. 10.3906/sag-2003-259
MLA ÇALIŞKANER Zihni Onur,Abdul Waheed Abdullah,TUZLAKOGLU OZTURK MERVE,Oymak Yeşim,TAZEBAY UYGAR HALIS,akar nejat,Kandilci Ayten,Ozkan Didem Identification of novel TUBB1 variants in patients with macrothrombocytopenia. Turkish Journal of Medical Sciences, vol.51, no.2, 2021, ss.490 - 500. 10.3906/sag-2003-259
AMA ÇALIŞKANER Z,Abdul Waheed A,TUZLAKOGLU OZTURK M,Oymak Y,TAZEBAY U,akar n,Kandilci A,Ozkan D Identification of novel TUBB1 variants in patients with macrothrombocytopenia. Turkish Journal of Medical Sciences. 2021; 51(2): 490 - 500. 10.3906/sag-2003-259
Vancouver ÇALIŞKANER Z,Abdul Waheed A,TUZLAKOGLU OZTURK M,Oymak Y,TAZEBAY U,akar n,Kandilci A,Ozkan D Identification of novel TUBB1 variants in patients with macrothrombocytopenia. Turkish Journal of Medical Sciences. 2021; 51(2): 490 - 500. 10.3906/sag-2003-259
IEEE ÇALIŞKANER Z,Abdul Waheed A,TUZLAKOGLU OZTURK M,Oymak Y,TAZEBAY U,akar n,Kandilci A,Ozkan D "Identification of novel TUBB1 variants in patients with macrothrombocytopenia." Turkish Journal of Medical Sciences, 51, ss.490 - 500, 2021. 10.3906/sag-2003-259
ISNAD ÇALIŞKANER, Zihni Onur vd. "Identification of novel TUBB1 variants in patients with macrothrombocytopenia". Turkish Journal of Medical Sciences 51/2 (2021), 490-500. https://doi.org/10.3906/sag-2003-259