Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation

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Tuominen , S , Juvonen , V , Amberla , K , Jolma , T , Rinne , JO , Tuisku , S , Kurki , T , Marttila , R , Pöyhönen , M , Savontaus , ML , Viitanen , M & Kalimo , H 2001 , ' Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation ' , Stroke , vol. 32 , no. 8 , pp. 1767-1774 . https://doi.org/10.1161/01.STR.32.8.1767

Title: Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation
Author: Tuominen, S; Juvonen, V.; Amberla, K; Jolma, T; Rinne, JO; Tuisku, S; Kurki, T; Marttila, R; Pöyhönen, M; Savontaus, ML; Viitanen, M; Kalimo, H
Contributor organization: HUSLAB
Date: 2001-08
Language: eng
Number of pages: 8
Belongs to series: Stroke
ISSN: 0039-2499
DOI: https://doi.org/10.1161/01.STR.32.8.1767
URI: http://hdl.handle.net/10138/329832
Abstract: Background and Purpose-CADASIL is an autosomal dominant arteriopathy, characterized by multiple brain infarcts, cognitive decline, and finally dementia, which is caused by mutations in Notch3 gene encoding a Notch3 receptor protein. We describe the clinical, neuropsychological, imaging, genetic, and skin biopsy findings in a CADASIL patient homozygous for the C475T mutation resulting in R133C amino acid substitution, in comparison to 9 age-matched heterozygous patients with the same mutation. Methods-The patients were examined clinically and neuropsychologically and with MRI and positron emission tomography for assessment of cerebral blood flow. The gene defect was analyzed by sequencing the products of polymerase chain reaction of exons 3 and 4 of the Notch3 gene. Dermal arteries were analyzed electron microscopically. Results-The homozygous patient had his first-ever stroke at age 28 years. This is markedly earlier than the average, but the patient's heterozygous son had his first transient ischemic attack-like episode at the same age and another heterozygous patient had his first-ever stroke when only 2 years older. He was neuropsychologically more severely deteriorated than all but 1 of the heterozygous patients. These 2 patients had the most severe (confluent grade D) white matter MRI changes. Positron emission tomography showed markedly reduced cerebral blood flow. Skin biopsy revealed profuse deposits of granular osmiophilic material. The progression of disease in the homozygous case was, however, slower than in the most severely affected heterozygous patient. Conclusions-Our homozygous patient's phenotype is within the clinical spectrum of CADASIL, although at its severe end. Thus, CADASIL may follow the classic definition of a dominant disease, according to which the heterozygous and homozygous patients are clinically indistinguishable.
Subject: CADASIL
dementia, vascular
homozygote
magnetic resonance imaging
neuropsychological tests
tomography, emission computed
HUNTINGTONS-DISEASE
DEMENTIA
SPECTRUM
INFARCTS
LESIONS
MRI
3112 Neurosciences
3124 Neurology and psychiatry
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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