Arg133Cys mutation of Notch3 in two unrelated Japanese families with CADASIL.
Intern Med
; 39(9): 732-7, 2000 Sep.
Article
em En
| MEDLINE
| ID: mdl-10969905
ABSTRACT
OBJECTIVE:
More than 80 unrelated, but all Caucasian, patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), originating from various communities around the world, have been molecularly identified. To clarify the occurrence of CADASIL in Orientals, we investigated Japanese families presenting as CADASIL.METHODS:
We performed the PCR-SSCP and sequence analyses using genomic DNA, isolated from venous blood of participants under informed consent. PATIENTS We identified two unrelated Japanese families with CADASIL, including 5 affected members through 2 generations.RESULTS:
Each of the affected individuals developed recurrent strokes without risk factors resulting in progressive dementia, pseudobulbar palsy, and gait disturbances which started after the fifth decade of life. Although affected individuals had no vascular risk factors, they showed various degrees of narrowing of retinal arteries. Their MRI/CTs showed characteristics of the disease; bilateral small infarcts in the thalamus, basal ganglia, brain stem, and deep white matter in addition to the findings of leukoaraiosis. On SPECT imaging, there was severe hypoperfusion in the cortex as well as in the white matter. Ultrastructural studies revealed an abnormal deposition of granular osmiophilic materials (GOM) within the basal lamina of pericytes in muscular capillaries. On PCR-SSCP and sequence analyses, a heterozygous Arg133Cys mutation was present, in the affected individuals, in the exon 4 of Notch3 gene which is the hot spot region for CADASIL mutations in Caucasian families. None of the non-affected members nor the 50 Japanese normal controls revealed this mutation.CONCLUSION:
Thus, our results confirm that CADASIL is a geographically widespread disorder caused by a Notch3 mutation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Demência por Múltiplos Infartos
/
Proteínas Proto-Oncogênicas
/
Mutação Puntual
/
Receptores de Superfície Celular
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Intern Med
Assunto da revista:
MEDICINA INTERNA
Ano de publicação:
2000
Tipo de documento:
Article