De novo mutation in the Notch3 gene causing CADASIL.
CADASIL, an autosomal dominant arteriopathy responsible for stroke and dementia, is caused by strongly stereotyped mutations in the Notch3 gene. We report a patient with a condition strongly suggestive of CADASIL (migraine, stroke, and white matter abnormalities), except that this patient did not have any first-degree relatives with similar symptoms. This patient carried a heterozygous Arg182Cys mutation in the Notch3 gene; this mutation was absent in his two biological parents. These data demonstrate the occurrence of a de novo noninherited mutation in the Notch3 gene, which indicates that CADASIL should not be rejected in the absence of a family history. Therefore, our finding suggests that CADASIL may be more frequent than anticipated.
Joutel
A
A
INSERM U25, Faculté de Médecine Necker-Enfants Malades, and Hopital Lariboisière, Paris, France.
Dodick
D D
DD
Parisi
J E
JE
Cecillon
M
M
Tournier-Lasserve
E
E
Bousser
M G
MG
D001921:Brain / Q000473:pathology; D015161:Dementia, Multi-Infarct / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012867:Skin / Q000473:pathology / Q000648:ultrastructure
C499374:NOTCH3 protein, human; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch