On the diagnosis of CADASIL.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic arteriopathy related to Notch3 mutations, is difficult to diagnosis. The goal of this study was to determine the value of clinical, immunohistochemical, and molecular techniques for the diagnosis of CADASIL. Clinical features and the immunohistochemical and molecular findings in 200 subjects with suspected CADASIL in whom 93 biopsies and 190 molecular studies are reported. Eighteen pathogenic mutations of the Notch3 gene, six of them previously unreported, were detected in 67 patients. The clinical features did not permit differentiation between CADASIL and CADASIL-like syndromes. The sensitivity and specificity of the skin biopsies was 97.7% and 56.5%, respectively, but increased to 100% and 81.5%, respectively, in cases with proven family history. In conclusion, a clinical diagnosis of CADASIL is difficult to determine and confirmatory techniques should be used judiciously.
Ampuero
Israel
I
Banco de Tejidos para Investigaciones Neurológicas (BTIN), Facultad de Medicina, Universidad Commplutense de Madrid, Madrid, Spain. fuinvesn@med.ucm.es
Alegre-Abarrategui
Javier
J
Rodal
Izaskun
I
España
Antonio
A
Ros
Raquel
R
Sendón
José Luis Lopez
JL
Galloway
Eva García
EG
Cervelló
Angeles
A
Caminero
Ana Belén
AB
Zabala
Antxon
A
Erro
Elena
E
Jarauta
Fernando
F
Morlán
Lorenzo
L
López-Valdés
Eva
E
Aladro
Yolanda
Y
Seijo
Manuel
M
Rivas
Guillermo García
GG
Muñoz
David G
DG
de Yébenes
Justo García
JG
D000368:Aged; D001706:Biopsy; D001921:Brain / Q000473:pathology*; D046589:CADASIL / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology*; D013030:Spain / Q000453:epidemiology; D011795:Surveys and Questionnaires
C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch