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

2020 ◽  
Vol 50 (6) ◽  
pp. 1573-1579
Author(s):  
Özge AKSEL KILIÇARSLAN ◽  
Esra ATAMAN ◽  
Semra GÜRSOY ◽  
Gürkan GÜRBÜZ ◽  
Aycan ÜNALP ◽  
...  
Keyword(s):  
Focal Cortical Dysplasia ◽  
Cortical Development ◽  
Gene Mutations ◽  
Genetic Alterations ◽  
Clinical Findings ◽  
Imaging Findings ◽  
Malformations Of Cortical Development ◽  
Tubulin Gene ◽  
Multicenter Studies

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.

Pathologic Features of Dysplasia and Accompanying Alterations Observed in Surgical Specimens from Patients with Intractable Epilepsy

2004 ◽  
Vol 19 (3) ◽  
pp. 341-350 ◽  
Author(s):  
Akiyoshi Kakita ◽  
Shigeki Kameyama ◽  
Shintaro Hayashi ◽  
Hiroshi Masuda ◽  
Hitoshi Takahashi
Keyword(s):  
White Matter ◽  
Focal Cortical Dysplasia ◽  
Molecular Layer ◽  
Cortical Development ◽  
Neurofibrillary Tangle ◽  
Intractable Epilepsy ◽  
Clinical Findings ◽  
Cortical Layer ◽  
Pathologic Features ◽  
Cortical Dysplasias

Malformations caused by abnormalities of cortical development, or cortical dysplasias, were examined in surgical specimens from 108 patients with medically intractable epilepsy to determine the scope of histopathologic changes. The relevance of the clinical findings was also evaluated. Various types and degrees of dysplastic features were observed in various combinations, including architectural abnormalities, an increased number of neurons in the molecular layer and/or cortical layer II, neuronal clustering, an increased number of satellite oligodendrocytes, abnormal gyration, single and/or aggregates of heterotopic neurons in the white matter, and the appearance of cytologically abnormal cells, such as giant or dysmorphic neurons and balloon cells. In the temporal lobe specimens, microdysgenesis (corresponding to mild malformations caused by abnormalities of cortical development and type IA/B focal cortical dysplasias) was more frequently observed than Taylor-type focal cortical dysplasia (type IIA/B), whereas in the frontal lobe specimens, the frequency of occurrence of both types was even. The ages at seizure onset and surgery of patients with the latter type were significantly lower than those of patients with the former. On the other hand, prominent astrocytosis in the cortex and white matter was evident in all cases, and many corpora amylacea and neurofibrillary tangle—like inclusions were observed in a subset of cases. An ultrastructural investigation revealed dilatation of the postsynaptic dendritic spines and shafts in the cortex and features indicating the occurrence in the white matter of demyelination followed by remyelination. Thus, with regard to the epileptogenic lesions, although dysplastic changes constitute the pathogenetic basis, the overlapping subsequent degenerative processes involving synapses, dendrites, and axons might contribute to the development of epileptogenic processes. Astrocytes might also actively participate in the development of the pathogenesis of epilepsy. ( J Child Neurol 2005;20:341—350).

Epilepsies: Malformations of Cortical Development—Focal Cortical Dysplasia (FCD)

2019 ◽  
pp. 1157-1169
Author(s):  
Serge Weis ◽  
Michael Sonnberger ◽  
Andreas Dunzinger ◽  
Eva Voglmayr ◽  
Martin Aichholzer ◽  
...  
Keyword(s):  
Focal Cortical Dysplasia ◽  
Cortical Development ◽  
Cortical Dysplasia ◽  
Malformations Of Cortical Development

Interobserver and intraobserver reproducibility in focal cortical dysplasia (malformations of cortical development)

Epilepsia ◽  
2009 ◽  
Vol 50 (12) ◽  
pp. 2593-2598 ◽  
Author(s):  
Wendy A. Chamberlain ◽  
Mark L. Cohen ◽  
Kymberly A. Gyure ◽  
Bette K. Kleinschmidt-DeMasters ◽  
Arie Perry ◽  
...  
Keyword(s):  
Focal Cortical Dysplasia ◽  
Cortical Development ◽  
Cortical Dysplasia ◽  
Malformations Of Cortical Development ◽  
Intraobserver Reproducibility

scholarly journals MRI of focal cortical dysplasia

2021 ◽  
Author(s):  
Horst Urbach ◽  
Elias Kellner ◽  
Nico Kremers ◽  
Ingmar Blümcke ◽  
Theo Demerath
Keyword(s):  
Molecular Genetics ◽  
Focal Cortical Dysplasia ◽  
Cortical Development ◽  
Cortical Dysplasia ◽  
Added Value ◽  
7 Tesla ◽  
Type I ◽  
Type Ii ◽  
Malformations Of Cortical Development ◽  
7 Tesla Mri

AbstractFocal cortical dysplasia (FCD) are histopathologically categorized in ILAE type I to III. Mild malformations of cortical development (mMCD) including those with oligodendroglial hyperplasia (MOGHE) are to be integrated into this classification yet. Only FCD type II have distinctive MRI and molecular genetics alterations so far. Subtle FCD including FCD type II located in the depth of a sulcus are often overlooked requiring the use of dedicated sequences (MP2RAGE, FLAWS, EDGE) and/or voxel (VBM)- or surface-based (SBM) postprocessing. The added value of 7 Tesla MRI has to be proven yet.

Role of Gene Mutations in Adult Acute Myeloid Leukemia Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3373-3373
Author(s):  
Sheng-Chieh Chou ◽  
Jih-Luh Tang ◽  
Liang-In Lin ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Genetic Alterations ◽  
Prognostic Impact ◽  
Hematopoietic Stem ◽  
Wbc Count ◽  
Acute Myeloid

Abstract Abstract 3373 Poster Board III-261 Purpose Several gene mutations had been found to have clinical implications in patients with acute myeloid leukemia (AML), especially in those with normal karyotype. However, the role of such gene mutations for AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) was unclear and inconclusive. We retrospectively evaluated the prognostic impact of 8 gene mutations in adult AML patients undergoing allo-HSCT. Materials & Methods From 1995 to 2007, a total of 463 consecutive adult patients with de novo non-M3 AML had comprehensive gene mutation analyses at the National Taiwan University Hospital. Three hundred and twenty five patients who received conventional induction chemotherapy were enrolled in this study. Those who received only low dose chemotherapy or palliative treatment were excluded. The genetic alterations analyzed included NPM1, FLT3/ITD, FLT3/TKD, CEBPA, AML1/RUNX1, RAS, MLL/PTD, and WT1. The clinical implication of these genetic alterations in the patients receiving allo-HSCT was analyzed, and the result was compared with that in patients without allo-HSCT. Results The clinical characteristics in the patients receiving allo-HSCT (n=100) and those without (n=225) were similar with the exception of age, being younger in the former group (35.4 years vs. 49.5 years p<0.001). In univariate analysis, older age (Age > 45 years), higher initial WBC count (WBC>50K/μL), elevated LDH level, unfavorable karyotype, FLT3/ITD, mutations of AML1/RUNX1 were significantly associated with poorer overall survival (OS) in patients not receiving allo-HSCT; While NPM1mut/FLT3ITDneg and CEBPA mutations served as significantly good prognostic indicators. In multivariate analysis, age, WBC count, karyotype, FLT3/ITD, AML1/RUNX1, CEBPA and NPM1mut/FLT3ITDneg remained to be independent prognostic factors in non-allo-HSCT patients. However, in patients receiving allo-HSCT, only unfavorable karyotype and disease status (refractory or remission) at the time of transplantation were associated with poorer OS both in univariate and multivariate analyses. The similar prognostic impact of FLT3/ITD, CEBPA, AML1/RUNX1 and NPM1 on OS was not seen in patients receiving allo-HSCT. Furthermore, in contrast to its poor prognostic impact in non-allo-HSCT patients, mutation of AML1/RUNX1 was a significant good prognostic factor for relapse free survival (p=0.046), although not for OS, in allo-HSCT group. Conclusion FLT3/ITD, mutations of AML1/RUNX1, CEBPA and NPM1 have great prognostic implication for OS in AML patients not receiving allo-HSCT. However, their impact on OS is ameliorated in patients receiving allo-HSCT. The results need to be confirmed by further studies on more patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Functional validation of genetic variants identified by next generation sequencing in malformations of cortical development

2021 ◽  
Author(s):  
Dalila De Vita
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Cortical Development ◽  
Next Generation ◽  
Malformations Of Cortical Development ◽  
Functional Studies ◽  
Generation Sequencing ◽  
In Vitro Treatment

Malformations of cortical development (MCDs) result from a disruption in the process of the human brain cortex formation: currently, there are no pharmacological treatments for diffuse MCDs. Next-generation sequencing has accelerated the identification of MCDs causing genes: in some cases, functional studies are needed to clarify the role of genetic variants. The aim of this PhD project has been to apply a multidisciplinary approach to identify causative mutations in patients with MCDs, validate the pathogenic role of the identified mutations, and assess the effectiveness of novel in vitro treatment for mTOR pathway related MCDs.

Sign in / Sign up

Export Citation Format

Share Document