Monogenic Vessel Diseases Related to Ischemic Stroke: A Clinical Approach

Ballabio, E.; Bersano, Anna; Bresolin, Nereo; Candelise, Livia

doi:10.1038/sj.jcbfm.9600520

Cited by 35 publications

(19 citation statements)

References 122 publications

(164 reference statements)

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“…other rare monogenetic vessel diseases like pseudoxanthoma elasticum [23], as well as hypertensive fibrohyalinosis [24] or increased cerebral blood flow of other etiology have to be taken into account.…”

Section: Discussionmentioning

confidence: 99%

Basilar Artery Diameter Is a Potential Screening Tool for Fabry Disease in Young Stroke Patients

Fellgiebel¹,

Keller²,

Martus³

et al. 2010

Cerebrovasc Dis

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Background: Fabry disease (FD) is a rare hereditary lysosomal storage disease that has been highlighted as a possible etiology of stroke at a young age. Enlarged basilar artery diameters (BADs) have been demonstrated in FD, and we hypothesize that they might be useful for the screening of FD in young stroke patients. The aim of this study was to compare BADs of young stroke patients without FD to those of FD patients and of healthy age-matched controls. Methods: BADs were measured using MR angiography in 3 age- and gender-matched groups: 25 FD patients (aged 36.5 ± 11.0 years), 26 non-FD stroke patients and 20 healthy controls. Results: Compared to the non-FD stroke patients, FD patients had significantly enlarged BADs. FD patients could be significantly separated from stroke patients by BADs (area under the curve = 0.89, 95% confidence interval 0.81–0.98). Eighty-six percent of all subjects could be correctly classified by BADs (sensitivity 84%, specificity 88.5%). Conclusions: Enlarged BADs were able to detect FD within a cohort of FD, stroke patients and healthy controls. BAD measurement could be an easily obtainable and sensitive screening tool for FD in young stroke patients.

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Section: Discussionmentioning

confidence: 99%

Basilar Artery Diameter Is a Potential Screening Tool for Fabry Disease in Young Stroke Patients

Fellgiebel¹,

Keller²,

Martus³

et al. 2010

Cerebrovasc Dis

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“…Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal dominant adult-onset disorder, belonging to the hereditary cerebral small vessel diseases (SVD), with predominant involvement of central nervous system (CNS) and retina [1][2][3]. RVCL encompasses three major conditions: Cerebroretinal Vasculopathy (CRV) [4], hereditary vascular retinopathy (HVR) [5,6] and hereditary endotheliopathy, retinopathy, nephropathy and stroke (HERNS) [7], found to be associated with C-terminal heterozygous frameshift (fs) mutations in the human 3 0 -5 0 DNA exonuclease TREX1 [8], normally located in the cytoplasm and translocated into the nucleus following oxidative DNA insult [9].…”

Section: Introductionmentioning

confidence: 99%

TREX1 C-terminal frameshift mutations in the systemic variant of retinal vasculopathy with cerebral leukodystrophy

et al. 2014

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Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an adult-onset disorder caused by C-terminal heterozygous frameshift (fs) mutations in the human 3'-5' DNA exonuclease TREX1. Hereditary systemic angiopathy (HSA) is considered a variant of RVCL with systemic involvement of unknown genetic cause, described in a unique family so far. Here we describe the second case of RVCL with systemic involvement, characterized by cerebral calcifications and pseudotumoral lesions, retinopathy, osteonecrosis, renal and hepatic failure. The genetic screening of TREX1 in this patient revealed the novel heterozygous T270fs mutation on the C-terminal region. On the same gene, we found the V235fs mutation, formerly shown in RVCL, in one patient previously reported with HSA. These mutations lead to important alterations of the C-terminal of the protein, with the loss of the transmembrane helix (T270fs) and the insertion of a premature stop codon, resulting in a truncated protein (V235fs). Functional analysis of T270fs-mutated fibroblasts showed a prevalent localization of the protein in the cytosol, rather than in the perinuclear region. RVCL with systemic involvement is an extremely rare condition, whose diagnosis is complex due to multiorgan manifestations, unusual radiological and histopathological findings, not easily attributable to a single disease. It should be suspected in young adults with systemic microangiopathy involving retina, liver, kidney, bones and brain. Here we confirm the causative role played by TREX1 autosomal dominant fs mutations disrupting the C-terminal of the protein, providing a model for the study of stroke in young adults.

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“…Several studies suggest that the AT1 receptor might be involved in hypertension. A polymorphism located in the 3 untranslated region of the AT1 receptor gene (AT1) (corresponding to an adenine/cytosine (A/C) base substitution at the 1166 position) has been shown to modify the association of the I/D ACE polymorphism with the occurrence of myocardial infarction [31].…”

Section: Fabry's Diseasementioning

confidence: 99%

“…This disorder is redesignated as CHARIOT (cerebral hereditary angiopathy with vascular retinopathy and impaired organ function caused by TREX1 mutations). Specific treatment options other than antiplatelet are not available [31][32][33][34].…”

Section: Autosomal Dominant Retinal Vasculopathy With Cerebral Leukodmentioning

confidence: 99%

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Cerebral Small Vessel Disease Clinical, Neuropsychological, and Radiological Phenotypes, Histopathological Correlates, and Described Genotypes: A Review

Issac

Chandra

Christopher

et al. 2015

Journal of Geriatrics

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Introduction. Vascular cognitive impairment is a common yet preventable cause for dementia. It needs high degree of suspicion and appropriate designing of investigatory tools to confirm diagnosis, identify comorbidities, and ascertain the areas of impairment. Commonly DSM-IV criterion is applied for diagnosis and detailed clinical and neuropsychological examination for identifying the specific phenotype is used. Early diagnosis using the mandatory criteria will help in early initiation of disease modifying treatment strategies which can result in partial reversal of vascular changes and arrest of progression. Patients with young onset disease might require genetic characterization for designing more aggressive treatment.Discussion and Conclusion. Dementias as such carry poor course and prognosis resulting in severe Disability Adjusted Life Years (DALYs) for patients and caregivers. Therefore, it is mandatory to identify treatable and preventable causes so that man power loss can be reduced.

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Monogenic Vessel Diseases Related to Ischemic Stroke: A Clinical Approach

Cited by 35 publications

References 122 publications

Basilar Artery Diameter Is a Potential Screening Tool for Fabry Disease in Young Stroke Patients

Basilar Artery Diameter Is a Potential Screening Tool for Fabry Disease in Young Stroke Patients

TREX1 C-terminal frameshift mutations in the systemic variant of retinal vasculopathy with cerebral leukodystrophy

Cerebral Small Vessel Disease Clinical, Neuropsychological, and Radiological Phenotypes, Histopathological Correlates, and Described Genotypes: A Review

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