| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Departments of Clinical Neuroscience (Drs. Markus, Martin, and Dong, and N. Ali) and Medical Genetics (M. Simpson and Dr. Crosby), St. George’s Hospital Medical School, and Department of Neuroscience (Dr. Powell), Institute of Psychiatry, Guy’s, King’s and St. Thomas’ School of Medicine, London, UK.
Address correspondence and reprint requests to Professor Hugh Markus, Department of Clinical Neuroscience, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK; e-mail: h.markus{at}sghms.ac.uk
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited autosomal dominant condition characterized by migraine, recurrent stroke, and dementia. It results from mutations in the notch3 gene but mutations may occur at multiple sites making molecular diagnosis time consuming. It has been suggested that the presence of granular osmiophilic material (GOM) on skin biopsy and involvement of the anterior temporal lobe and external capsule on MRI may help in diagnosis.
Methods: The authors identified 83 potential index cases from the British population and screened exons 2 to 23 of notch3. MRI scans were scored using a modified Scheltens scale. Skin biopsy was performed in a subgroup.
Results: Fifteen different point mutations were identified in 48 families, 73% of which were in exon 4, 8% in exon 3, and 6% in each of exons 5 and 6. Moderate or severe involvement of the anterior temporal pole on MRI had a sensitivity of 89% and specificity of 86% for diagnosis of CADASIL, whereas external capsule involvement had a high sensitivity of 93% but a low specificity of 45%. Skin biopsy, performed in 18 cases, had a sensitivity of 45% and specificity of 100%.
Conclusions: The spectrum of mutations in this study can be used to plan appropriate screening protocols; a suggested protocol is to screen exon 4, and proceed to exons 3, 5, and 6 where indicated. GOM on skin biopsy is diagnostic but can be negative. Anterior temporal pole involvement on MRI is a useful diagnostic marker.
This article has been cited by other articles:
|
|
 |
|
  M. Monet-Lepretre, B. Bardot, B. Lemaire, V. Domenga, O. Godin, M. Dichgans, E. Tournier-Lasserve, M. Cohen-Tannoudji, H. Chabriat, and A. Joutel Distinct phenotypic and functional features of CADASIL mutations in the Notch3 ligand binding domain Brain, June 1, 2009; 132(6): 1601 - 1612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yamamoto, M. Ihara, C. Tham, R. W.C. Low, J. Y. Slade, T. Moss, A. E. Oakley, T. Polvikoski, and R. N. Kalaria Neuropathological Correlates of Temporal Pole White Matter Hyperintensities in CADASIL Stroke, June 1, 2009; 40(6): 2004 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mykkanen, M. Junna, K. Amberla, L. Bronge, H. Kaariainen, M. Poyhonen, H. Kalimo, and M. Viitanen Different Clinical Phenotypes in Monozygotic CADASIL Twins With a Novel NOTCH3 Mutation Stroke, June 1, 2009; 40(6): 2215 - 2218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tikka, K. Mykkanen, M.-M. Ruchoux, R. Bergholm, M. Junna, M. Poyhonen, H. Yki-Jarvinen, A. Joutel, M. Viitanen, M. Baumann, et al. Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients Brain, April 1, 2009; 132(4): 933 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M L Stromillo, M T Dotti, M Battaglini, M Mortilla, S Bianchi, K Plewnia, L Pantoni, D Inzitari, A Federico, and N De Stefano Structural and metabolic brain abnormalities in preclinical cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy J. Neurol. Neurosurg. Psychiatry, January 1, 2009; 80(1): 41 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Taylor and G. A. Doody CADASIL: a guide to a comparatively unrecognised condition in psychiatry Advan. Psychiatr. Treat., September 1, 2008; 14(5): 350 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Malandrini, C. Gaudiano, S. Gambelli, G. Berti, G. Serni, S. Bianchi, A. Federico, and M. T. Dotti DIAGNOSTIC VALUE OF ULTRASTRUCTURAL SKIN BIOPSY STUDIES IN CADASIL Neurology, April 24, 2007; 68(17): 1430 - 1432. [Full Text] [PDF]
|
|
|
|
|
|
S. Saiki, K. Sakai, M. Saiki, Y. Kitagawa, T. Umemori, K. Murata, M. Matsui, and G. Hirose Varicose veins associated with CADASIL result from a novel mutation in the Notch3 gene. Neurology, July 25, 2006; 67(2): 337 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Singhal, P. Rich, and H. S. Markus The Spatial Distribution of MR Imaging Abnormalities in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy and Their Relationship to Age and Clinical Features AJNR Am. J. Neuroradiol., November 1, 2005; 26(10): 2481 - 2487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Peters, C. Opherk, T. Bergmann, M. Castro, J. Herzog, and M. Dichgans Spectrum of Mutations in Biopsy-Proven CADASIL: Implications for Diagnostic Strategies Arch Neurol, July 1, 2005; 62(7): 1091 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M T Dotti, A Federico, R Mazzei, S Bianchi, O Scali, F L Conforti, T Sprovieri, D Guidetti, U Aguglia, D Consoli, et al. The spectrum of Notch3 mutations in 28 Italian CADASIL families J. Neurol. Neurosurg. Psychiatry, May 1, 2005; 76(5): 736 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S S M Razvi, R Davidson, I Bone, and K W Muir The prevalence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the west of Scotland J. Neurol. Neurosurg. Psychiatry, May 1, 2005; 76(5): 739 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Opherk, N. Peters, J. Herzog, R. Luedtke, and M. Dichgans Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients Brain, November 1, 2004; 127(11): 2533 - 2539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Markus Genes for stroke J. Neurol. Neurosurg. Psychiatry, September 1, 2004; 75(9): 1229 - 1231. [Full Text] [PDF]
|
|
|
|
|
|
S. Singhal, S. Bevan, T. Barrick, P. Rich, and H. S. Markus The influence of genetic and cardiovascular risk factors on the CADASIL phenotype Brain, September 1, 2004; 127(9): 2031 - 2038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E L Sampson, J D Warren, and M N Rossor Young onset dementia Postgrad. Med. J., March 1, 2004; 80(941): 125 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O'Sullivan, P. M. Rich, T. R. Barrick, C. A. Clark, and H. S. Markus Frequency of Subclinical Lacunar Infarcts in Ischemic Leukoaraiosis and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy AJNR Am. J. Neuroradiol., August 1, 2003; 24(7): 1348 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.S. M. Razvi, R. Davidson, I. Bone, K.W. Muir, S. A. J. L. Oberstein, and H. Markus Diagnostic strategies in CADASIL Neurology, June 24, 2003; 60(12): 2019 - 2020. [Full Text] [PDF]
|
|
|
|
|
|
Y. Dong, A. Hassan, Z. Zhang, D. Huber, C. Dalageorgou, H. S. Markus, D. Inzitari, and C. Sarti Yield of Screening for CADASIL Mutations in Lacunar Stroke and Leukoaraiosis Stroke, January 1, 2003; 34(1): 203 - 206. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
