PSEN1/SLC20A2 double mutation causes early-onset Alzheimer's disease and primary familial brain calcification co-morbidity.
Alzheimer’s disease
Cognitive disorder
Dementia
Movement disorder
Neurogenetics
Neuroscience
Primary familial brain calcification
Journal
Neurogenetics
ISSN: 1364-6753
Titre abrégé: Neurogenetics
Pays: United States
ID NLM: 9709714
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
30
04
2023
accepted:
07
06
2023
medline:
6
7
2023
pubmed:
21
6
2023
entrez:
21
6
2023
Statut:
ppublish
Résumé
Primary familial brain calcification (PFBC; formerly Fahr's disease) and early-onset Alzheimer's disease (EOAD) may share partially overlapping pathogenic principles. Although the heterozygous loss-of-function mutation c.1523 + 1G > T in the PFBC-linked gene SLC20A2 was detected in a patient with asymmetric tremor, early-onset dementia, and brain calcifications, CSF β-amyloid parameters and FBB-PET suggested cortical β-amyloid pathology. Genetic re-analysis of exome sequences revealed the probably pathogenic missense mutation c.235G > A/p.A79T in PSEN1. The SLC20A2 mutation segregated with mild calcifications in two children younger than 30 years. We thus describe the stochastically extremely unlikely co-morbidity of genetic PFBC and genetic EOAD. The clinical syndromes pointed to additive rather than synergistic effects of the two mutations. MRI data revealed the formation of PFBC calcifications decades before the probable onset of the disease. Our report furthermore exemplifies the value of neuropsychology and amyloid PET for differential diagnosis.
Identifiants
pubmed: 37341843
doi: 10.1007/s10048-023-00723-x
pii: 10.1007/s10048-023-00723-x
pmc: PMC10319679
doi:
Substances chimiques
Sodium-Phosphate Cotransporter Proteins, Type III
0
SLC20A2 protein, human
0
PSEN1 protein, human
0
Presenilin-1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
209-213Informations de copyright
© 2023. The Author(s).
Références
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