A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms

Abstract Cerebral cavernous malformation (CCM) is a vascular lesion of the central nervous system that may lead to distinct symptoms among patients including cerebral hemorrhages, epileptic seizures, focal neurologic deficits, and/or headaches. Disease-related mutations were identified previously in...

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Autores principales:	Hilal Eren Gozel, Kıvanç Kök, Fatma Ozlen, Cihan Isler, Sadrettin Pence
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69d50fc2f4924f18886c4604605f0649
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spelling	oai:doaj.org-article:69d50fc2f4924f18886c4604605f06492021-12-02T19:16:59ZA novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms10.1038/s41598-021-98647-92045-2322https://doaj.org/article/69d50fc2f4924f18886c4604605f06492021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98647-9https://doaj.org/toc/2045-2322Abstract Cerebral cavernous malformation (CCM) is a vascular lesion of the central nervous system that may lead to distinct symptoms among patients including cerebral hemorrhages, epileptic seizures, focal neurologic deficits, and/or headaches. Disease-related mutations were identified previously in one of the three CCM genes: CCM1, CCM2, and CCM3. However, the rate of these mutations in sporadic cases is relatively low, and new studies report that mutations in CCM genes may not be sufficient to initiate the lesions. Despite the growing body of research on CCM, the underlying molecular mechanism has remained largely elusive. In order to provide a novel insight considering the specific manifested symptoms, CCM patients were classified into two groups (as Epilepsy and Hemorrhage). Since the studied patients experience various symptoms, we hypothesized that the underlying cause for the disease may also differ between those groups. To this end, the respective transcriptomes were compared to the transcriptomes of the control brain tissues and among each other. This resulted into the identification of the differentially expressed coding genes and the delineation of the corresponding differential expression profile for each comparison. Notably, some of those differentially expressed genes were previously implicated in epilepsy, cell structure formation, and cell metabolism. However, no CCM1-3 gene deregulation was detected. Interestingly, we observed that when compared to the normal controls, the expression of some identified genes was only significantly altered either in Epilepsy (EGLN1, ELAVL4, and NFE2l2) or Hemorrhage (USP22, EYA1, SIX1, OAS3, SRMS) groups. To the best of our knowledge, this is the first such effort focusing on CCM patients with epileptic and hemorrhagic symptoms with the purpose of uncovering the potential CCM-related genes. It is also the first report that presents a gene expression dataset on Turkish CCM patients. The results suggest that the new candidate genes should be explored to further elucidate the CCM pathology. Overall, this work constitutes a step towards the identification of novel potential genetic targets for the development of possible future therapies.Hilal Eren GozelKıvanç KökFatma OzlenCihan IslerSadrettin PenceNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hilal Eren Gozel Kıvanç Kök Fatma Ozlen Cihan Isler Sadrettin Pence A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms
description	Abstract Cerebral cavernous malformation (CCM) is a vascular lesion of the central nervous system that may lead to distinct symptoms among patients including cerebral hemorrhages, epileptic seizures, focal neurologic deficits, and/or headaches. Disease-related mutations were identified previously in one of the three CCM genes: CCM1, CCM2, and CCM3. However, the rate of these mutations in sporadic cases is relatively low, and new studies report that mutations in CCM genes may not be sufficient to initiate the lesions. Despite the growing body of research on CCM, the underlying molecular mechanism has remained largely elusive. In order to provide a novel insight considering the specific manifested symptoms, CCM patients were classified into two groups (as Epilepsy and Hemorrhage). Since the studied patients experience various symptoms, we hypothesized that the underlying cause for the disease may also differ between those groups. To this end, the respective transcriptomes were compared to the transcriptomes of the control brain tissues and among each other. This resulted into the identification of the differentially expressed coding genes and the delineation of the corresponding differential expression profile for each comparison. Notably, some of those differentially expressed genes were previously implicated in epilepsy, cell structure formation, and cell metabolism. However, no CCM1-3 gene deregulation was detected. Interestingly, we observed that when compared to the normal controls, the expression of some identified genes was only significantly altered either in Epilepsy (EGLN1, ELAVL4, and NFE2l2) or Hemorrhage (USP22, EYA1, SIX1, OAS3, SRMS) groups. To the best of our knowledge, this is the first such effort focusing on CCM patients with epileptic and hemorrhagic symptoms with the purpose of uncovering the potential CCM-related genes. It is also the first report that presents a gene expression dataset on Turkish CCM patients. The results suggest that the new candidate genes should be explored to further elucidate the CCM pathology. Overall, this work constitutes a step towards the identification of novel potential genetic targets for the development of possible future therapies.
format	article
author	Hilal Eren Gozel Kıvanç Kök Fatma Ozlen Cihan Isler Sadrettin Pence
author_facet	Hilal Eren Gozel Kıvanç Kök Fatma Ozlen Cihan Isler Sadrettin Pence
author_sort	Hilal Eren Gozel
title	A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms
title_short	A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms
title_full	A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms
title_fullStr	A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms
title_full_unstemmed	A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms
title_sort	novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/69d50fc2f4924f18886c4604605f0649
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A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms

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