The first two authors contributed equally to this work.
CADASIL: Extended polymorphisms and mutational analysis of the NOTCH3 gene
Article first published online: 11 NOV 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 87, Issue 5, pages 1162–1167, April 2009
How to Cite
Ungaro, C., Mazzei, R., Conforti, F.L., Sprovieri, T., Servillo, P., Liguori, M., Citrigno, L., Gabriele, A.L., Magariello, A., Patitucci, A., Muglia, M. and Quattrone, A. (2009), CADASIL: Extended polymorphisms and mutational analysis of the NOTCH3 gene. J. Neurosci. Res., 87: 1162–1167. doi: 10.1002/jnr.21935
- Issue published online: 23 FEB 2009
- Article first published online: 11 NOV 2008
- Manuscript Accepted: 19 SEP 2008
- Manuscript Revised: 12 JUN 2008
- Manuscript Received: 3 MAR 2008
- Italian Ministero dell'Istruzione, dell'Università e della Ricerca. Grant Number: MIUR-FIRB2006-RBIP06PMF2_006
- NOTCH3 gene
CADASIL is a cerebrovascular disease caused by mutations in the NOTCH3 gene. Most mutations result in a gain or loss of cysteine residue in one of the 34 epidermal growth factor-like repeats in the extracellular domain of the Notch3 protein, thus sparing the number of cysteine residues. To date, more than 130 different mutations in the NOTCH3 gene have been reported in CADASIL patients, of which 95% are missense point mutations. Many polymorphisms have also been identified in the NOTCH3 coding sequence, some of them leading to amino acid substitutions. The aim of the present study was to analyze the NOTCH3 gene in a large group of patients affected by leukoencephalopathy and to investigate the presence of genetic variants. The molecular analysis revealed several nucleotide alterations. In particular, we identified 20 different mutations, 22 polymorphisms, and 8 genetic variants of unknown pathological significance never reported previously. We hope that this NOTCH3 gene mutational analysis, performed in such a significant number of unrelated and related patients affected by leukoencephalopathy, will help in molecular screening for the NOTCH3 gene, thus contributing to enlargement of the NOTCH3 gene variation database. © 2008 Wiley-Liss, Inc.