Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease.
Presenilin 1 (PSEN1) gene mutations are found in 30-70% of familial early-onset Alzheimer disease (EOAD) cases (onset <60 years). Prevalence of these mutations is highly variable including ethnic differences worldwide. No Peruvian kindred with familial AD (FAD) have been described. Standardized clinical evaluation and cognitive assessment were completed in a Peruvian family with severe EOAD. Clinical course was characterized by very early onset (before age 35 years), progressive cognitive impairment with early memory loss, spatial disorientation and executive dysfunction. We sequenced all exons of PSEN1 in the proband and identified a c.475C>G DNA change resulting in a p.L153V missense mutation in the transmembrane domain 2 of the gene. This mutation is also present in the three additional affected siblings but not in a non-affected family member consistent with segregation of this mutation with the disease. This is the first report of a Peruvian family affected with EOAD associated with a PSEN1 mutation. This same mutation has been reported previously in English and French families, but a novel variants very close to the mutation and ancestry informative markers analysis suggests the mutation might be of Amerindian or African origin in this Peruvian family.
Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru; Northern Pacific Global Health Research Fellows Training Consortium, Bethesda, MD, United States. Electronic address: mario.cornejo.o@incngen.org.pe.
Mario R
MR
Cornejo-Olivas
Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States.
Chang-En
CE
Yu
Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru; School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru.
Pilar
P
Mazzetti
Parkinson's Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States; Department of Neurology, University of Washington, Seattle, WA, United States.
Ignacio F
IF
Mata
School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru.
Maria
M
Meza
Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru.
Saul
S
Lindo-Samanamud
Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States; Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States; Parkinson's Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States; Department of Neurology, University of Washington, Seattle, WA, United States; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States.
James B
JB
Leverenz
Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States; Parkinson's Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States; Department of Neurology, University of Washington, Seattle, WA, United States; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States.
Thomas D
TD
Bird
D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D053764:Presenilin-1 / Q000235:genetics*
C508853:PSEN1 protein, human; D053764:Presenilin-1
Early-onset Alzheimer's disease; Peruvian; Presenilin-1