Investigation of the most common clinical and imaging findings and the role of tubulin genes in the etiology of malformations of cortical development

Authors: ÖZGE AKSEL KILIÇARSLAN, ESRA ATAMAN, SEMRA GÜRSOY, GÜRKAN GÜRBÜZ, AYCAN ÜNALP, PINAR GENÇPINAR, NİHAL OLGAÇ DÜNDAR, SELVİNAZ EDİZER, AYFER ÜLGENALP, ÖZLEM GİRAY BOZKAYA

Abstract: Background and aim: The number of reports on the role of tubulin gene mutations (TUBA1A, TUBB2B, and TUBB3) in etiology of malformations of cortical development has peaked in recent years. We aimed to determine tubulin gene defects on a patient population with simple and complex malformations of cortical development, and investigate the relationship between tubulin gene mutations and disease phenotype. Materials and methods: We evaluated 47 patients with simple or complex malformations of cortical development, as determined by radiological examination, for demographic features, clinical findings and mutations on TUBA1A, TUBB2B, and TUBB3 genes. Results: According to the magnetic resonance imaging findings, 19 patients (40.5%) had simple malformations of cortical development and 28 (59.5%) patients had complex malformations of cortical development. Focal cortical dysplasia was the most common simple malformation, lissencephaly was the most common coexisting cortical malformation, and corpus callosum anomalies were the most common coexisting extracortical neurodevelopmental abnormalities. None of the patients had genetic alterations on TUBA1A, TUBB2B, and TUBB3 genes causing protein dysfunction. On the other hand, the frequencies of some polymorphisms were higher when compared to the literature. Conclusion: It is crucial to identify the etiology in patients with malformations of cortical development in order to provide appropriate genetic counseling and prenatal diagnosis. We consider that multicenter studies with higher patient numbers and also including other malformations of cortical development-related genes are required to determine underlying etiological factors of malformations of cortical development patients.

Keywords: Cortical dysplasia, tubulinopathies, TUBA1A, TUBB2B, TUBB3

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