Prion protein codon 129 polymorphism modifies age at onset of frontotemporal dementia with the C.709-1G>A progranulin mutation.
Frontotemporal lobar degeneration because of mutations in the progranulin (PGRN) gene presents a high variability both in the clinical phenotype and age of onset of disease. Factors that influence this variability remain largely unknown. The aim of our study was to determine whether selected genetic variables modify age at onset of disease in our series of 21 patients with a single splicing mutation (c.709-1G>A) in the PGRN gene, all of whom were of Basque descent. In our analysis, we included the following genetic variables: PGRN rs5848 and rs9897526 polymorphisms, APOE and microtubule-associated protein tau genotypes, and PRNP codon 129 polymorphism. We found no association between PGRN polymorphisms, APOE and microtubule-associated protein tau genotypes, and age at onset of the disease; whereas we report evidence for an association between PRNP codon 129 polymorphism and age at onset of disease in frontotemporal dementia-PGRN(+) patients. MM homozygous carriers presented onset of disease on average 8.5 years earlier than patients who carried at least 1 valine on their PRNP codon 129 (MV or VV). The biological justification for this association remains speculative.
Moreno
Fermín
F
Department of Neurology, Hospital Donostia, San Sebastian, Gipuzkoa, Spain. FERMIN.MORENOIZCO@osakidetza.net
Alzualde
Ainhoa
A
Camblor
Pablo Martínez
PM
Barandiaran
Myriam
M
Van Deerlin
Vivianna M
VM
Gabilondo
Alazne
A
Martí Massó
José F
JF
López de Munain
Adolfo
A
Indakoetxea
Begoña
B
D017668:Age of Onset; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D000077153:Progranulins; D020133:Reverse Transcriptase Polymerase Chain Reaction
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D000077153:Progranulins