Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese

Lee, Yi‐Chung; Liu, Chin‐San; Chang, Ming-Hong; Lin, Kon‐Ping; Fuh, Jong Ling; Lu, Yi-Chu; Liu, Yafen; Soong, Bing‐Wen

doi:10.1007/s00415-009-0091-3

Cited by 73 publications

(92 citation statements)

References 24 publications

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“…Also, hyperintensities of the anterior temporal pole, considered a characteristic magnetic resonance imaging (MRI) feature in CADASIL, are found less often in East Asian patients [8,9,10]. The majority of East Asian patients with CADASIL carry the same R544C mutation [7,8,9]. However, R544C mutation has rarely been reported as a site of mutations in Caucasian patients [11].…”

Section: Introductionmentioning

confidence: 99%

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Cognitive Profile of CADASIL Patients with R544C Notch3 Mutation

2014

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Background: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. In the present study, we aimed to analyze cognitive and neuroimaging profiles of CADASIL patients with R544C mutation. Methods: Fifty-eight consecutive patients with R544C mutation and 26 normal controls were investigated. The patients were divided into two groups depending on the presence (CADASIL with dementia: CADASIL-D) or absence of dementia (CADASIL no dementia: CADASIL-ND). We applied the same neuropsychological test to the three groups. Brain magnetic resonance images were obtained from 58 patients with R544C mutation. Linear regression models were used to assess the impact of lacunes and white matter hyperintensities on cognitive function in the CADASIL-ND group. Results: Compared to controls, the CADASIL-ND group demonstrated significant difficulties concerning measures of attention, executive function, and motor control. The CADASIL-D group was impaired in all cognitive domains that were assessed, except the language domain. After correction for age and educational level, the number of lacunes was associated with lower scores in the Alzheimer's Disease Assessment Scale cognitive subtest and Stroop color test in the CADASIL-ND group. Conclusions: Non-Caucasian CADASIL patients with R544C mutation and Caucasian CADASIL patients show similar patterns of cognitive impairment.

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Section: Introductionmentioning

confidence: 99%

“…East Asian patients have higher rates of intracranial hemorrhage (ICH) than Caucasian patients [7,8]. Also, hyperintensities of the anterior temporal pole, considered a characteristic magnetic resonance imaging (MRI) feature in CADASIL, are found less often in East Asian patients [8,9,10].…”

Section: Introductionmentioning

confidence: 99%

Cognitive Profile of CADASIL Patients with R544C Notch3 Mutation

2014

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“…Although some features were more frequent among CADASIL patients than in NOTCH3 -negative patients, none were pathognomonic [14]. The differences in clinical presentations, MRI features and high prevalence of vascular risk factors were suggested to increase the difficulty of differential diagnoses [15,16]. Here we recruited all patients analyzed for targeted NOTCH3 mutation in 10 stroke centers from Turkey and investigated the variability of clinical and radiological features in CADASIL and NOTCH3 -negative patients.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Radiological Features in CADASIL and <b><i>NOTCH3</i></b>-Negative Patients: A Multicenter Study from Turkey

İnce

Benbir²,

Síva³

et al. 2014

Eur Neurol

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Background: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. Methods: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. Results: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). Conclusion: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.

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“…Migraine is very frequent initial symptom in European CADASIL patients 1,11 while intracerebral hemorrhage is more common in Asians especially in those with arterial hypertension 3 . In the presented family the clinical presentation and an abnormal neurological finding was present in all but one family members with the mutation.…”

Section: Discussionmentioning

confidence: 99%

“…There is a large spectrum of CADASIL mutations. More than hundred different mutations in 18 exons have been already described 1,[3][4][5] . In European population exon 4 is the most frequently involved site of the NOTCH3 gene mutations, followed by exon 8 and 3 (ref.…”

Section: Introductionmentioning

confidence: 99%

Clinical spectrum in CADASIL family with a new mutation

Peisker¹,

Musil²,

Hřebı́ček³

et al. 2013

BIOMED PAP

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Background. Clinical presentation of CADASIL patients is variable due to the impact of other vascular risk factors and the type of a NOTCH3 mutation. This variability may impede the diagnosis of the disease. Subjects and Methods. We report a comprehensive evaluation of several individuals in the CADASIL family whose member was identified to have the new mutation of NOTCH3 receptor on exon 6 (p. G296C). We performed genetic testing, clinical and neuropsychological examination, cerebral MRI, Doppler sonography of cerebral arteries, fundoscopic examination and fluorescent angiography in six family members to determine the corresponding clinical spectrum associated with the new mutation. Results and Conclusion. The CADASIL mutation was detected in four individuals. Three of them were symptomatic, two having a history of stroke and one suffering from migraine. Although individuals had heterogeneous findings, the common feature included vascular changes that were present on cerebral and/or retinal arteries in all the mutation carriers even in one subject without clinical manifestation of the disease.

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Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese

Cited by 73 publications

References 24 publications

Cognitive Profile of CADASIL Patients with R544C Notch3 Mutation

Cognitive Profile of CADASIL Patients with R544C Notch3 Mutation

Clinical and Radiological Features in CADASIL and <b><i>NOTCH3</i></b>-Negative Patients: A Multicenter Study from Turkey

Clinical spectrum in CADASIL family with a new mutation

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