TY  - JOUR
AU  - Zimmermann, Milan
AU  - Mengel, David
AU  - Raupach, Katrin
AU  - Haack, Tobias
AU  - Neumann, Manuela
AU  - Synofzik, Matthis
TI  - Frequency and neuropathology of HTT repeat expansions in FTD/ALS: co-existence rather than causation.
JO  - Journal of neurology
VL  - 272
IS  - 1
SN  - 0367-004X
CY  - Heidelberg
PB  - Springer
M1  - DZNE-2024-01419
SP  - 58
PY  - 2025
AB  - While ≥ 40 CAG repeat expansions in HTT present a well-established cause of Huntington's disease (HD), an enrichment of HTT repeat expansions was recently reported also in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), including FTD/ALS patients with additional HD neuropathology. This raises the question whether the phenotypic spectrum of HTT expansions can be extended to ALS and FTD, and whether HTT should be considered as a new causative gene of FTD/ALS. If HTT repeat expansions were indeed systematically related to FTD/ALS, one would expect an increased frequency of HTT carriers in FTD/ALS, who can clinically/neuropathologically not be explained better than by the presence of the HTT repeat expansions.Screening of HTT repeat expansions in 249 consecutive patients with ALS or FTD by short-read genome sequencing took place. The post-mortem neuropathological examination was performed in the identified HTT repeat expansion carrier.One HTT repeat expansion [40/22 repeats (± 1)] was identified in an ALS patient, giving a frequency of 0.4
KW  - Humans
KW  - Frontotemporal Dementia: genetics
KW  - Frontotemporal Dementia: pathology
KW  - Amyotrophic Lateral Sclerosis: genetics
KW  - Amyotrophic Lateral Sclerosis: pathology
KW  - Male
KW  - Female
KW  - Huntingtin Protein: genetics
KW  - Middle Aged
KW  - Aged
KW  - Trinucleotide Repeat Expansion: genetics
KW  - Brain: pathology
KW  - Brain: diagnostic imaging
KW  - ALS (Other)
KW  - Amyotrophic lateral sclerosis (Other)
KW  - Frontotemporal dementia (Other)
KW  - HTT (Other)
KW  - Huntington (Other)
KW  - MAPT (Other)
KW  - Huntingtin Protein (NLM Chemicals)
KW  - HTT protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11638390
C6  - pmid:39666103
DO  - DOI:10.1007/s00415-024-12822-2
UR  - https://pub.dzne.de/record/273945
ER  -