title: Putative role of specific JAG1 gene exons in modulating clinical features in patients with leukoencephalopathy.
abstract: The aim of this study was to investigate the possible role of JAG1 gene mutations in modulating clinical features in patients with CADASIL-like phenotype which resulted negative for NOTCH3 gene mutations. Sixty-six CADASIL-like patients without NOTCH3 gene mutations were investigated for 5 out of 26 exons of the JAG1 gene, whose mutations were implicated in central nervous system vascular abnormalities. PCR was performed with primers specific for exons 3, 4, 13, 23 and 24 comprising the intron-exon boundaries. Amplicons were then analyzed by denaturing high performance liquid chromatography (DHPLC). The exons showing a variant DHPLC profile were directly sequenced. The sequence of exons 3, 4 and 23 revealed the presence of four already described polymorphisms in JAG1. 1001C/T (g.16015 C>T) in exon 4 was found in 9 patients, IVS23+18delT (g.33147 delT) in 29 patients, IVS3-15T/C (g.15852 T>C) in 17 patients, IVS2-43C/T (g.10532 C>T) in 1 patient; both the polymorphism 1001C/T and IVS3-15T/C were found in 3 patients. No mutations were found. These data demonstrate absence of correlation between mutations in specific JAG1 gene exons and clinical features in patients with CADASIL-like phenotype.
authors: Institute of Neurological Sciences, National Research Council, 87050 Mangone, Cosenza, Italy.
authors: Carmine
authors: C
authors: Ungaro
authors: Teresa
authors: T
authors: Sprovieri
authors: Francesca L
authors: FL
authors: Conforti
authors: Maria
authors: M
authors: Muglia
authors: Alessandra
authors: A
authors: Patitucci
authors: Angela
authors: A
authors: Magariello
authors: Anna L
authors: AL
authors: Gabriele
authors: Aldo
authors: A
authors: Quattrone
authors: Rosalucia
authors: R
authors: Mazzei
mesh_terms: D001927:Brain Diseases / Q000235:genetics*; D046589:CADASIL / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D005091:Exons / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics; D000072099:Serrate-Jagged Proteins
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins