 |
|
A Novel Mutation in the Notch3 Gene in an Italian Family With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Genetic and Magnetic Resonance Spectroscopic Findings
Rosario L. Oliveri, MD, MSc;
Maria Muglia, PhD;
Nicole De Stefano, MD, PhD;
Rosalucia Mazzei, PhD;
Angelo Labate, MD;
Francesca L. Conforti, PhD;
Allessandra Patitucci, PhD;
Anna L. Gabriele, PhD;
Giuseppe Tagarelli, PhD;
Angela Magariello, PhD;
Mario Zappia, MD;
Antonio Gambardella, MD;
Antonio Federico, MD;
Aldo Quattrone, MD
Arch Neurol. 2001;58:1418-1422.
Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL) is a hereditary syndrome caused by mutations
of the Notch3 gene, usually localized to exons 3
and 4.
Objectives To report a novel pathogenetic mutation occurring in exon 6 of the Notch3 gene, a location not previously recognized in patients
with CADASIL, and to report the results of magnetic resonance spectroscopy
in CADASIL.
Methods Mutation analysis of the Notch3 gene was performed
in 2 patients belonging to a large kindred manifesting CADASIL, as well as
in 7 clinically unaffected members of the family and 200 control chromosomes.
Proton magnetic resonance spectroscopy was used to estimate metabolite resonance
intensities in the 2 affected subjects.
Results Sequence analysis of the Notch3 gene showed
a new missense mutation CGC TGC in codon 332 of exon 6, resulting in
the replacement of an arginine residue with a cysteine. This mutation was
never observed in the 7 unaffected members of the family and the 200 control
chromosomes examined. Proton magnetic resonance spectroscopy showed a diffuse
decrease in cerebral N-acetylaspartate, indicating
the presence of widespread axonal damage.
Conclusions Our findings emphasize the role of direct DNA sequence analysis for
the diagnosis of CADASIL. Moreover, the results of proton magnetic resonance
spectroscopy suggest that widespread axonal damage may be an early finding
of the disease.
From the Institute of Neurology, University Magna Græcia, Catanzaro,
Italy (Drs Oliveri, Labate, Zappia, Gambardella, and Quattrone); Institute
of Experimental Medicine and Biotechnology, National Research Council, Mangone,
Italy (Drs Oliveri, Muglia, Mazzei, Conforti, Patitucci, Gabriele, Tagarelli,
Magariello, Gambardella, and Quattrone); and Department of Neurological Sciences,
University of Siena, Siena, Italy (Drs De Stefano and Federico).
Dr
Oliveri died February 25, 2001.
Corresponding author and reprints: Aldo Quattrone, MD, Clinica Neurologica,
Policlinico Universitario Mater Domini, Via T. Campanella, 115, 88100 Catanzaro,
Italy (e-mail: neurol.unicz{at}interbusiness.it).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
Archives of Neurology Reader's Choice: Continuing Medical Education
Arch Neurol. 2001;58(9):1503-1504.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
The spectrum of Notch3 mutations in 28 Italian CADASIL families
Dotti et al.
J. Neurol. Neurosurg. Psychiatry 2005;76:736-738.
ABSTRACT
| FULL TEXT
A novel Notch3 gene mutation not involving a cysteine residue in an Italian family with CADASIL
Mazzei et al.
Neurology 2004;63:561-564.
ABSTRACT
| FULL TEXT
Recurrent hemiplegia, normal MRI, and NOTCH3 mutation in a 14-year-old: Is this early CADASIL?
Golomb et al.
Neurology 2004;62:2331-2332.
FULL TEXT
|
