NOTCH3 mutation involving three cysteine residues in a family with typical CADASIL.
Mutations in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke and vascular dementia. All CADASIL mutations identified so far result in the loss or gain of one cysteine residue within epidermal growth factor (EGF)-like repeat domains. Here an in-frame deletion causing a loss of three cysteine residues within EGF repeat 6 is reported. These data are consistent with the hypothesis that the change toward an odd number of cysteine residues within a given EGF repeat and therefore an unpaired, reactive cysteine residue is the common and critical molecular event in CADASIL.
Dichgans
M
M
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany. mdichgans@nefo.med.uni-muenchen.de
Herzog
J
J
Gasser
T
T
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D015161:Dementia, Multi-Infarct / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012091:Repetitive Sequences, Nucleic Acid
C499374:NOTCH3 protein, human; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D003545:Cysteine