Mutations of the notch3 gene in non-caucasian patients with suspected CADASIL syndrome.
The Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). To investigate the genetic contribution of Notch mutations in familial cases with vascular leukoencephalopathy, we screened 13 patients from 11 unrelated families, which were selected on the basis of magnetic resonance imaging findings and positive family history. We identified three different missense mutations in 5 patients from 4 families. Two (Arg90Cys and Arg133Cys) are the same as previously reported in Caucasian patients, the other (Cys174Phe) is a novel mutation causing a loss of a cysteine in epidermal-growth-factor-like repeats of Notch3. These data indicate that the CADASIL Notch3 mutations were found in approximately 35% of familial cases with leukoencephalopathy, suggesting genetic heterogeneity of the disease.
Department of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.
S
S
Kotorii
K
K
Takahashi
K
K
Kamimura
T
T
Nishio
K
K
Arima
H
H
Yamada
E
E
Uyama
M
M
Uchino
A
A
Suenaga
M
M
Matsumoto
G
G
Kuchel
G A
GA
Rouleau
T
T
Tabira
D000328:Adult; D000368:Aged; D053938:DNA Fragmentation / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D015161:Dementia, Multi-Infarct / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D017422:Sequence Analysis, DNA; D012833:Siloxanes
D017931:DNA Primers; C499374:NOTCH3 protein, human; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012833:Siloxanes; C402373:poly(methylhydrosiloxane)