Phenotypic Features of Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Subjects with R544C Mutation
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Background and PurposeCerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most-common single gene disorder of cerebral small vessel disease. There is no definite evidence of genotype-phenotype correlation in CADASIL. However, recent studies have shown the unique phenotypic feature of NOTCH3 R544C mutation. MethodsWe investigated the phenotypic spectrum of NOTCH3 R544C mutation in 73 CADASIL patients in Jeju between April 2012 and January 2014. ResultsOf the 73 subjects from 60 unrelated families included in this study, 40 (55%) were men. The mean age of the subjects was 62.2± 12.2 (range 34–86 years). Cerebral infarction was the most frequent manifestation (37%), followed by cognitive impairment (32%), headache (17%), psychiatric symptom (16%), intracerebral hemorrhage (12%), transient ischemic attack (7%), and seizure (1%). The mean age of the subjects with ischemic or hemorrhagic episodes was 64.9±10.9 (range 41–86 years). A diagnosis of dementia was made in 12 subjects (16%). The mean age of the subjects with dementia was 75.6±6.5 (range 62–86 years). About 3% of subjects were unable to walk without assistance at assessment. Only one subject had developed chronic headache before the 40s. ConclusionsOur data support the hypothesis that CADASIL patients with R544C mutation in Jeju have relatively late onset disease.
Abstract
Background and PurposeCerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most-common single gene disorder of cerebral small vessel disease. There is no definite evidence of genotype-phenotype correlation in CADASIL. However, recent studies have shown the unique phenotypic feature of NOTCH3 R544C mutation. MethodsWe investigated the phenotypic spectrum of NOTCH3 R544C mutation in 73 CADASIL patients in Jeju between April 2012 and January 2014. ResultsOf the 73 subjects from 60 unrelated families included in this study, 40 (55%) were men. The mean age of the subjects was 62.2± 12.2 (range 34–86 years). Cerebral infarction was the most frequent manifestation (37%), followed by cognitive impairment (32%), headache (17%), psychiatric symptom (16%), intracerebral hemorrhage (12%), transient ischemic attack (7%), and seizure (1%). The mean age of the subjects with ischemic or hemorrhagic episodes was 64.9±10.9 (range 41–86 years). A diagnosis of dementia was made in 12 subjects (16%). The mean age of the subjects with dementia was 75.6±6.5 (range 62–86 years). About 3% of subjects were unable to walk without assistance at assessment. Only one subject had developed chronic headache before the 40s. ConclusionsOur data support the hypothesis that CADASIL patients with R544C mutation in Jeju have relatively late onset disease.
참고문헌 (20)
- Joutel A, "Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia", Nature, 383, pp.707~710 (1996)
- Ghosh M, "Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy", Ann Neurol, 78, pp.887~900 (2015)
- Chabriat H, "Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy", Lancet, 346, pp.934~939 (1995)
- Lee JS, "Clinical significance of cerebral microbleeds locations in CADASIL with R544C NOTCH3mutation", PLoS One, 10, pp.e0118163~ (2015)
- Liao YC, "Characterization of CADASIL among the Han Chinese in Taiwan: distinct genotypic and phenotypic profiles", PLoS One, 10, pp.e0136501~ (2015)
- Chabriat H, "Cadasil", Lancet Neurol, 8, pp.643~653 (2009)
- Adib-Samii P, "Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype : study in 200 consecutively recruited individuals", Stroke, 41, pp.630~634 (2010)
- Lee JH, "Development of the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet(CERAD-K) : clinical and neuropsychological assessment batteries", J Gerontol B Psychol Sci Soc Sci, 57, pp.47~53 (2002)
- Oberstein SA, "Diagnostic Notch3 sequence analysis in CADASIL:three new mutations in Dutch patients", Neurology, 52, pp.1913~1915 (1999)
- Opherk C, "Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients", Brain, 127(Pt 11), pp.2533~2539 (2004)
- Mykkänen K, "Detection of the founder effect in Finnish CADASIL families", Eur J Hum Genet, 12, pp.813~819 (2004)
- Bianchi S, "CADASIL in central Italy : a retrospective clinical and genetic study in 229 patients", J Neurol, 262, pp.134~141 (2015)
- Liu X, "The genetic spectrum and the evaluation of CADASIL screening scale in Chinese patients with NOTCH3 mutations", J Neurol Sci, 354, pp.63~69 (2015)
- Ueda A, "Genotypic and phenotypic spectrum of CADASIL in Japan : the experience at a referral center in Kumamoto University from 1997 to 2014", J Neurol, 262, pp.1828~1836 (2015)
- Kim YE, "Spectrum of NOTCH3 mutations in Korean patients with clinically suspicious cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy", Neurobiol Aging, 35, pp.726.e1~726.e6 (2014)
- Vahedi K, "Migraine with aura and brain magnetic resonance imaging abnormalities in patients with CADASIL", Arch Neurol, 61, pp.1237~1240 (2004)
- Chabriat H, "Autosomal dominant migraine with MRI white-matter abnormalities mapping to the CADASIL locus", Neurology, 45, pp.1086~1091 (1995)
- Choi JC, "Headache among CADASIL patients with R544C mutation : prevalence, characteristics, and associations", Cephalalgia, 34, pp.22~28 (2014)
- Dichgans M, "The phenotypic spectrum of CADASIL : clinical findings in 102 cases", Ann Neurol, 44, pp.731~739 (1998)
- 이정석, "R544C Mutation을 가진 CADASIL 환자의 혈관성 위험인자", Dementia and Neurocognitive Disorders(대한치매학회지), 8(2), pp.98~103 (2009), 대한치매학회