Dement Neurocogn Disord.  2016 Jun;15(2):52-54. 10.12779/dnd.2016.15.2.52.

Possible Role of a Missense Mutation of p.P167S on NOTCH3 Gene Associated with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

• Choi BW
• Park S
• Kim HJ

• KMID: 2442856
• DOI: http://doi.org/10.12779/dnd.2016.15.2.52

Abstract

BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disorder caused by mutations in the NOTCH3 gene, located on chromosome 19p13. NOTCH3 encodes a transmembrane receptor which plays a role in cellular differentiation and cell cycle regulation.
CASE REPORT
A 71-year-old female showing headache and memory impairment, familial history of stroke and having a missense mutation from proline to serine at codon 167 in the exon 4 on NOTCH3 gene. Five family members revealed the same mutation (c.499C>T), who presented migrainous headache and stroke. In this study, we have uncovered a novel NOTCH3 mutation at the nucleotide position 499 (c.499C>T; p.P167S) in a family with CADASIL.
CONCLUSIONS
We suggested a missense mutation of proline to serine at codon 167 in exon 4 of the NOTCH3 gene, which resulted in the substitution of cytosine to thymine (c.499C>T) resulting migraine, stroke and vascular cognitive impairment.

Keyword

cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; c.499C>T; p.P167S

MeSH Terms

Aged
CADASIL*
Cell Cycle
Codon
Cognition Disorders
Cytosine
Exons
Female
Headache
Humans
Memory
Migraine Disorders
Mutation, Missense*
Proline
Serine
Stroke
Thymine
Codon
Cytosine
Proline
Serine
Thymine

Figure

• 

  Fig. 1 A: Pedigree of a family with c.499C>T mutation. Black arrow (II.3) indicates the proband. Filled symbols indicate individuals who had stroke. Analysis of exon 4 of the NOTCH3 gene performed on five family members (II.6, II.7, II.9, III.1, III.2). Proband (II.3), her sister (II.6) and first-born son (III.1) had a novel c.499C>T mutation. B: Magnetic resonance imaging (fluid attenuation inversion recovery) revealed bilateral hyperintensities in the periventricular, subcortical and left external capsular white matter. C: Gradient recalled echo showed microbleeds at the right temporal and parietal lobe (arrows). D: Magnetic resonance imaging (fluid attenuation inversion recovery) revealed hyperintensities in the subcortical and right external capsular white matter (open arrows) in first-born son. E: Sequencing of NOTCH3 in this family revealed a heterozygous C-to-T substitution at nucleotide position 499, which changes a proline to serine at codon 167 (c.499C>T; p.P167S). The proband's first-born son and sibling had the same mutation.

Reference

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