Abstract | BACKGROUND: OBJECTIVES: To identify the spectrum of NOTCH3 mutations in CADASIL and to discuss the implications for diagnostic strategies. DESIGN: Screening for NOTCH3 mutations was performed in 125 unrelated German CADASIL patients with biopsy-proven disease by direct sequencing of exons coding for epidermal growth factor-like repeats. Results were compared with those of previously published studies. RESULTS: We detected 54 distinct mutations (117 missense mutations and 3 in-frame deletions) in 120 (96.0%) of the 125 patients. Of the mutations, 58.3% were located in exon 4 and 85.8% in exons 2 through 6. In 5 patients (4.0%), no mutation was identified. CONCLUSIONS: Almost 90% of mutations could be detected within a few exons (exons 2-6). Thus, genetic testing should initially be focused on these exons, with some variation depending on the population in whom it is being performed. Yet, genetic testing for CADASIL is associated with a nameable proportion of false-negative results. Cases with a high index of clinical suspicion should be investigated by skin biopsy if genetic testing is negative.
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Authors | Nils Peters, Christian Opherk, Tanja Bergmann, Mirna Castro, Jürgen Herzog, Martin Dichgans |
Journal | Archives of neurology
(Arch Neurol)
Vol. 62
Issue 7
Pg. 1091-4
(Jul 2005)
ISSN: 0003-9942 [Print] United States |
PMID | 16009764
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- NOTCH3 protein, human
- Proto-Oncogene Proteins
- Receptor, Notch3
- Receptors, Cell Surface
- Receptors, Notch
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Topics |
- Biopsy
- CADASIL
(genetics)
- DNA Mutational Analysis
- Exons
- Genetic Testing
- Humans
- Proto-Oncogene Proteins
(genetics)
- Receptor, Notch3
- Receptors, Cell Surface
(genetics)
- Receptors, Notch
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