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Genetic landscape of early-onset dementia in Hungary
Introduction Early-onset dementias (EOD) are predominantly genetically determined, but the underlying disease-causing alterations are often unknown. The most frequent forms of EODs are early-onset Alzheimer’s disease (EOAD) and frontotemporal dementia (FTD). Patients This study included 120 Hungaria...
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Published in: | Neurological sciences 2022-09, Vol.43 (9), p.5289-5300 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Introduction
Early-onset dementias (EOD) are predominantly genetically determined, but the underlying disease-causing alterations are often unknown. The most frequent forms of EODs are early-onset Alzheimer’s disease (EOAD) and frontotemporal dementia (FTD).
Patients
This study included 120 Hungarian patients with EOD (48 familial and 72 sporadic) which had a diagnosis of EOAD (
n
= 49), FTD (
n
= 49), or atypical dementia (
n
= 22).
Results
Monogenic dementia was detected in 15.8% of the patients. A pathogenic hexanucleotide repeat expansion in the
C9ORF72
gene was present in 6.7% of cases and disease-causing variants were detected in other known AD or FTD genes in 6.7% of cases (
APP
,
PSEN1
,
PSEN2
,
GRN
). A compound heterozygous alteration of the
TREM2
gene was identified in one patient and heterozygous damaging variants in the
CSF1R
and
PRNP
genes were detected in two other cases. In two patients, the coexistence of several heterozygous damaging rare variants associated with neurodegeneration was detected (1.7%). The
APOE
genotype had a high odds ratio for both the
APOE
ɛ4/3 and the ɛ4/4 genotype (OR = 2.7 (95%CI = 1.3–5.9) and OR = 6.5 (95%CI = 1.4–29.2), respectively). In
TREM2
,
SORL1
, and
ABCA7
genes, 5 different rare damaging variants were detected as genetic risk factors. These alterations were not present in the control group.
Conclusion
Based on our observations, a comprehensive, targeted panel of next-generation sequencing (NGS) testing investigating several neurodegeneration-associated genes may accelerate the path to achieve the proper genetic diagnosis since phenotypes are present on a spectrum. This can also reveal hidden correlations and overlaps in neurodegenerative diseases that would remain concealed in separated genetic testing. |
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ISSN: | 1590-1874 1590-3478 |
DOI: | 10.1007/s10072-022-06168-8 |