NOTCH3 Gene Mutation in a Chilean Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Family

Gallardo A.; Latapiat V.; Rivera A.; Fonseca B.; Roldan A.; Sandoval P.; Sánchez C.; Matamala, J. M.

Abstract

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.

Más información

Título según WOS: NOTCH3 Gene Mutation in a Chilean Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Family
Título según SCOPUS: NOTCH3 Gene Mutation in a Chilean Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Family
Título de la Revista: JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
Volumen: 29
Número: 2
Editorial: Elsevier
Fecha de publicación: 2020
Idioma: English
DOI:

10.1016/j.jstrokecerebrovasdis.2019.104530

Notas: ISI, SCOPUS