INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts
and leukoencephalopathy (CADASIL) is a rare hereditary stroke disorder caused by
mutations in the NOTCH3 gene. We report the first Chilean CADASIL family with
complete radiological and histological studies.
METHODS: The family tree was constructed from an autopsy-confirmed confirmed
patient, and includes 3 generations. We performed clinical, pathologic, genetic,
and radiologic examinations on members of a family with CADASIL.
RESULTS: In the second generation, findings compatible with CADASIL were
identified in 6 individuals, all of whom had a missense mutation in exon 3
(c.268C>T) resulting in an arginine to cysteine amino acid substitution at
position 90 (R90C). In the third generation, a missense mutation was detected in
one of the 4 asymptomatic individuals.
CONCLUSIONS: There are similarities in clinical presentation between this family
and previously described Asian and European series with R90C mutations.
Detecting genotypes with a gain or loss of cysteine residues opens the door to
future gene transfection-based therapies.