Abstract
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
(CADASIL) is an inherited cerebrovascular disease caused by a mutation of the NOTCH3 gene. The clinical information of two CADASIL families was studied and mutation analysis
of the NOTCH3 gene was performed by DNA direct sequencing. Published studies of Mainland Chinese
CADASIL patients were reviewed and reanalyzed. The patients in the two families showed
migraine with aura, stroke and cognitive decline. Cranial MRI revealed subcortical
white matter infarcts and leukoencephalopathy. Two previously reported mutations of
the NOTCH3 gene, c.397C>T and c.268C>T, were identified and cosegregated with the disease. The main clinical features,
cranial MRI and pathological changes in Mainland Chinese CADASIL patients were similar
to those in other regions. The frequency of migraine may be lower than that in Europe,
but similar to that in Asia. Eight different NOTCH3 gene mutations were reported among Mainland Chinese CADASIL patients; of these, the
c.322C>T mutation has not been reported in other regions. This study supports that the clinical
features of Mainland Chinese CADASIL patients are similar to those seen in other regions
and that exon 3 and exon 4 of the NOTCH3 gene are the mutation hotspots in Mainland Chinese CADASIL patients.
Keywords
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References
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12.Nat Genet. 1993; 3: 256-259
- NOTCH3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia.Nature. 1996; 383: 707-710
- Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.Lancet. 1995; 346: 934-939
- Autosomal dominant leukoencephalopathy and subcortical ischaemic stroke: a clinicopathological study.Stroke. 1993; 24: 122-125
- Systematic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.Acta Neuropathol. 1995; 89: 500-512
- Strong clustering and stereotyped nature of NOTCH3 mutations in CADASIL patients.Lancet. 1997; 350: 1511-1515
- Diagnostic NOTCH3 sequence analysis in CADASIL: three new mutations in Dutch patients. Dutch CADASIL Research Group.Neurology. 1999; 52: 1913-1915
- Screening British CADASIL families for mutations in the NOTCH3 gene.J Med Genet. 2000; 37: 224-225
- Diagnostic strategies in CADASIL.Neurology. 2003; 60: 2019-2020
- Detection of the founder effect in Finnish CADASIL families.Eur J Hum Genet. 2004; 12: 813-819
- Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies.Arch Neurol. 2005; 62: 1091-1094
- The spectrum of NOTCH3 mutations in 28 Italian CADASIL families.J Neurol Neurosurg Psychiatry. 2005; 76: 736-738
- Two novel Italian CADASIL families from Central Italy with mutation CGC–TGC at codon 1006 in the exon 19 NOTCH3 gene.Neurol Sci. 2006; 27: 252-256
- Diagnostic value of ultrastructural skin biopsy studies in CADASIL.Neurology. 2007; 68: 1430-1432
- A novel mutation (C67Y) in the NOTCH3 gene in a Korean CADASIL patient.J Korean Med Sci. 2003; 18: 141-144
- Characteristics of CADASIL in Korea: a novel cysteine-sparing NOTCH3 mutation.Neurology. 2006; 66: 1511-1516
- Intracerebral hemorrhages in CADASIL.Neurology. 2006; 67: 2042-2044
- Two novel mutations of the NOTCH3 gene in Korean patients with CADASIL.Mutat Res. 2006; 593: 116-120
- Identification of a NOTCH3 mutation in a Japanese CADASIL family. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.Alzheimer Dis Assoc Disord. 1999; 13: 222-225
- Two Japanese CADASIL families with a R141C mutation in the NOTCH3 gene.Intern Med. 2001; 40: 1144-1148
- Mutations of the NOTCH3 gene in non-Caucasian patients with suspected CADASIL syndrome.Dement Geriatr Cogn Disord. 2001; 2: 185-193
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and CADASIL-like disorders in Japan.Ann N Y Acad Sci. 2002; 977: 273-278
- Genetic, clinical and pathological studies of CADASIL in Japan: a partial contribution of NOTCH3 mutations and implications of smooth muscle cell degeneration for the pathogenesis.J Neurol Sci. 2003; 15: 79-84
- CADASIL with NOTCH3 S180C presenting anticipation of onset age and hallucinations.J Neurol Sci. 2005; 238: 87-91
- CADASIL with a novel mutation in exon 7 of NOTCH3 (C388Y).Intern Med. 2006; 45: 981-985
- Varicose veins associated with CADASIL result from a novel mutation in the NOTCH3 gene.Neurology. 2006; 67: 337-339
- Novel mutation of the NOTCH3 gene in a Japanese patient with CADASIL.Eur J Neurol. 2007; 14: 464-466
- Recurrent hemiplegia, normal MRI, and NOTCH3 mutation in a 14-year-old: is this early CADASIL?.Neurology. 2004; 62: 2331-2332
- Mutation of the NOTCH3 gene in a Thai cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy family.J Med Assoc Thai. 2003; 86: 178-182
- CADASIL syndrome in a large Turkish kindred caused by the R90C mutation in the NOTCH3 receptor.Eur J Neurol. 2002; 9: 23-28
- The R110C mutation in NOTCH3 causes variable clinical features in two Turkish families with CADASIL syndrome.J Neurol Sci. 2006; 246: 123-130
- CADASIL in Arabs: clinical and genetic findings.BMC Med Genet. 2007; 8: 67
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Chinese family: clinical, radiological and skin biopsy features.J Clin Neurosci. 2004; 11: 304-307
- A novel mutation (C271F) in the NOTCH3 gene in a Chinese man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.Clin Chim Acta. 2007; 376: 229-232
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: two novel mutations in the NOTCH3 gene in Chinese.J Neurol Sci. 2006; 246: 111-115
- Arg332Cys mutation of NOTCH3 gene in the first known Taiwanese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.J Neurol Sci. 2005; 228: 125-128
- NOTCH3 gene mutations in four Chinese families with cerebral autosomal dominant aeteriopathy with subcortical infarcts and leukoencephalopathy.Zhonghua Yixue Zazhi. 2004; 84: 1175-1180
- A study of subcortical infarcts and leukoencephalopathy (CADASIL) in a family with autosomal cerebral dominant arteriopathy.Zhonghua Nei Ke Za Zhi. 2004; 43: 924-927
- A case of CADASIL manifested as multiple sclerosis with literature review.Beijing Yixue. 2006; 28: 605-608
- Peripheral neuropathy in cerebral dominant arteriopathy with subcortical infarcts and leukoencephalopathy.Zhonghua Shenjing Ke Zazhi. 2007; 40: 675-677
- CADASIL: a review with proposed diagnostic criteria.Eur J Neurol. 1998; 5: 219-233
- Quantitative MRI in CADASIL: correlation with disability and cognitive performance.Neurology. 1999; 52: 1361-1367
- Positron emission tomography examination of cerebral blood flow and glucose metabolism in young CADASIL patients.Stroke. 2004; 35: 1603-1608
- MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL.Neurology. 2001; 56: 628-634
- Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.Acta Neuropathol (Berl). 1995; 89: 500-512
- Diagnostic strategies in CADASIL.Neurology. 2002; 59: 1134-1138
Article info
Publication history
Published online: January 27, 2009
Accepted:
December 9,
2008
Received in revised form:
December 7,
2008
Received:
July 1,
2008
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
