A novel mutation in PSEN1 (p.T119I)in an Argentine family with early- and late-onset Alzheimer's disease

ITZCOVICH, TATIANA; CHREM-MÉNDEZ, PATRICIO; VÁZQUEZ, SILVIA; BARBIERI-KENNEDY, MICAELA; NIIKADO, MATÍAS; MARTINETTO, HORACIO; ALLEGRI, RICARDO; SEVLEVER, GUSTAVO; SURACE, EZEQUIEL I.

NEUROBIOLOGY OF AGING

ELSEVIER SCIENCE INC

Año: 2019

0197-4580

Mutations in PSEN1 are the most common cause of early-onset Alzheimer´s disease (AD). In this article, we present an Argentine family with autosomal dominant early- and late-onset AD. The proband and 6 family members were available for genetic testing and clinical and neuropsychological assessments. Cerebrospinal fluid biomarkers were analyzed in the proband and a cousin (mutation carrier), who also underwent positron emission tomography using F-18-2-fluoro-2-deoxy-D-glucose and Pittsburgh compound B. Exon sequencing of PSEN1, PSEN2, and APP revealed a novel heterozygous variant in PSEN1 (c.356C>T; p.T119I). Median age of onset in the family was 56 years. However, the proband´s uncle showed initial symptoms at age 71. Although no DNA was available, he was an obligate carrier because his daughter (proband´s cousin)carried the mutation. Both the proband and his cousin exhibited biomarker evidence (cerebrospinal fluid or imaging)of underlying Alzheimer´s pathology. Overall, our results support that the PSEN1 p.T119I variant is likely pathogenic.