CCM1 and CCM2 variants in patients with cerebral cavernous malformation in an ethnically Chinese population in Taiwan

Chang, Chun‐Wei; Hsu, Peng‐Wei; Wei, Kuo‐Chen; Fung, Hon-Chung; Hsih, Mo-Song; Hsu, Wen‐Chuin; Ro, Long‐Sun; Chang, Chen-Nen; Wang, Jiun‐Jie; Wu, Yih‐Ru; Chen, Sien-Tsong

doi:10.1038/s41598-019-48448-y

Cited by 8 publications

(6 citation statements)

References 25 publications

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“…It is the first study to analyze the difference in the clinical course in three subgroups (assumed, confirmed, and non-FCCM). This pragmatic subgrouping is relevant because the vast majority of patients diagnosed with multiple CCM do not undergo genotyping [31][32][33] (13.4% in our cohort). In addition, the penetration of the disease is highly variable, meaning that, for example, a generation of an affected family may stay asymptomatic or undiagnosed.…”

Section: Discussionmentioning

confidence: 99%

Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non‐familial disease

Santos

Rauschenbach

Saban

et al. 2022

Euro J of Neurology

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Background and Purpose: Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. Methods: Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow-up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non-familial multiple cavernous malformations. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage and recurrent hemorrhage.Results: A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non-FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5-year follow-up (FU). The cumulative 5-year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non-FCCM cases.Conclusions: FCCM patients with ICH at diagnosis are prone to develop rebleeding.During untreated 5-year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non-FCCM patients showed an equal cumulative 5-year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.

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Section: Discussionmentioning

confidence: 99%

Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non‐familial disease

Santos

Rauschenbach

Saban

et al. 2022

Euro J of Neurology

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“…In contrast, almost 83% of mutations were located in exons 1-6, which may have an influence on the PTB domain. In Chinese population, there are about 10 CCM2 variants reported in familial and sporadic cases, 30% are delection, 20% are missense mutations, 20% are insertion mutations, and others are nonsense mutations, silent mutations and substitutions (1,6,(34)(35)(36). Among them, 30% are located on HHD (1,6,35).…”

Section: Discussionmentioning

confidence: 99%

“…CCMs can onset at any age but mostly occur between 20 and 50 years old (3,4). The main clinical manifestations are intracerebral hemorrhage (ICH) and seizures, and other symptoms include recurrent headaches, focal neurological deficits, vertigo, and paresis (5,6). MRI can be performed to diagnose CCMs.…”

Section: Introductionmentioning

confidence: 99%

A Novel CCM2 Gene Mutation Associated With Cerebral Cavernous Malformation

Liu

Zhang

2020

Front. Neurol.

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Cerebral cavernous malformations (CCMs) are the second most prevalent type of vascular malformation within the central nervous system. CCMs occur in two forms-sporadic and familial-the latter of which has an autosomal dominant mode of inheritance with incomplete penetrance and variable clinical expressivity. There are three genes considered to be associated with CCMs,-CCM1, which codes for KRIT1 protein; CCM2, which codes for MGC4607 protein; and CCM3, which codes for PDCD10 protein. To date, more than 74 gene mutations of CCM2 have been reported, and ∼45% are deletion mutations. In this article, we disclose a novel CCM2 genetic variant (c.755delC, p.S252fs * 40X) identified in a Chinese family to enrich the database of CCM2 genotypes.

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“…Potential risk factors for hemorrhage include sex (females > males), age, lesion location, size, trauma, perfusion, and prior hemorrhage [11,12]. Common clinical manifestations are intralesional or extralesional intracerebral hemorrhage with or without focal neurological deficits and seizures [8,13].…”

Section: Histological Examinationmentioning

confidence: 99%

De Novo Cavernoma in the Sensory Cortex Causing Cervicobrachialgia

Dhruv¹,

Michael²,

Sophie³

et al. 2020

Neurosurg Cases Rev

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most common cerebral vascular malformation after developmental venous anomaly and capillary telangiectasia [1]. Cavernomas are comprised of clusters of tightly packed, abnormally thin-walled blood vessels that displace normal neurological tissue in the brain or spinal cord [2]. Three gene mutations (CCM1, CCM2, and CCM3), which can either be inherited or occur sporadically, have been associated with the formation of cavernomasIntracerebral hemorrhage is the initial complication in 30% of cases [4,5]. Superficial cavernomas are associated with a lower risk of hemorrhage than those located in the depth. Patients with asymptomatic cavernomas with typical imaging findings are usually managed conservatively with serial imaging studies. Symptomatic patients may present with acute headache, epilepsy and acute or subacute neurological deficits owing to overt intra or extralesional hemorrhage [6].We report the case of a 32-year-old female who suffered from symptoms classified as cervicobrachialgia that were caused by a rapidly growing de novo cavernoma located in the post central gyrus.

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CCM1 and CCM2 variants in patients with cerebral cavernous malformation in an ethnically Chinese population in Taiwan

Cited by 8 publications

References 25 publications

Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non‐familial disease

Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non‐familial disease

A Novel CCM2 Gene Mutation Associated With Cerebral Cavernous Malformation

De Novo Cavernoma in the Sensory Cortex Causing Cervicobrachialgia

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