title: Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis.
abstract: CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is a small-artery disease of the brain caused by NOTCH3 mutations that lead to an abnormal accumulation of NOTCH3 within the vasculature. We aimed to establish whether immunostaining skin biopsy samples with a monoclonal antibody specific for NOTCH3 could form the basis of a reliable and easy diagnostic test. We compared the sensitivity and specificity of this method in two groups of patients suspected of having CADASIL with complete scanning of mutation-causing exons of NOTCH3 (in a retrospective series of 39 patients) and with limited scanning of four exons that are mutation hotspots (prospective series of 42 patients). In the retrospective series skin biopsy was positive in 21 (96%) of the 22 CADASIL patients examined and negative in all others; in the prospective series, seven of the 42 patients had a positive skin biopsy whereas only four had a mutation detected by limited NOTCH3 scanning. Our immunostaining technique is highly sensitive (96%) and specific (100%) for diagnosis of CADASIL.
authors.affiliation: INSERM EPI 99-21, Faculté de Médecine Lariboisière, 10 Avenue de Verdun, 75010, Paris, France. joutel@paris7.jussieu.fr
authors.forename: A
authors.initials: A
authors.lastname: Joutel
authors.forename: P
authors.initials: P
authors.lastname: Favrole
authors.forename: P
authors.initials: P
authors.lastname: Labauge
authors.forename: H
authors.initials: H
authors.lastname: Chabriat
authors.forename: C
authors.initials: C
authors.lastname: Lescoat
authors.forename: F
authors.initials: F
authors.lastname: Andreux
authors.forename: V
authors.initials: V
authors.lastname: Domenga
authors.forename: M
authors.initials: M
authors.lastname: Cécillon
authors.forename: K
authors.initials: K
authors.lastname: Vahedi
authors.forename: A
authors.initials: A
authors.lastname: Ducros
authors.forename: F
authors.initials: F
authors.lastname: Cave-Riant
authors.forename: M G
authors.initials: MG
authors.lastname: Bousser
authors.forename: E
authors.initials: E
authors.lastname: Tournier-Lasserve
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015161:Dementia, Multi-Infarct / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification*; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; C499374:NOTCH3 protein, human; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch