Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
To analyze the frequencies of major genetic variants and the clinical features in Finnish patients with amyotrophic lateral sclerosis (ALS) with or without the
hexanucleotide repeat expansion.
A cohort of patients with motor neuron disease was recruited between 1993 and 2020 at the Helsinki University Hospital and 2 second-degree outpatient clinics in Helsinki. Finnish ancestry patients with ALS fulfilled the diagnosis according to the revised El Escorial criteria and the Awaji-criteria. Two categories of familial ALS (FALS) were used. A patient was defined FALS-A if at least 1 first- or second-degree family member had ALS, and FALS-NP, if family members had additional neurologic or psychiatric endophenotypes.
Of the 815 patients, 25% had FALS-A and 45% FALS-NP.
expansion (
) was found in 256 (31%) of all patients, in 58% of FALS-A category, in 48% of FALS-NP category, and in 23 or 17% of sporadic cases using the FALS-A or FALS-NP definition.
or
p.D91A homozygosity was found in 328 (40%) of the 815 patients. We compared demographic and clinical characteristics between
and patients with unknown cause of ALS (
). We found that the age at onset was significantly earlier and survival markedly shorter in the
vs
patients with ALS. The shortest survival was found in bulbar-onset male
patients, whereas the longest survival was found in
limb-onset males. Older age at onset associated consistently with shorter survival in
and
patients in both limb-onset and bulbar-onset groups. There were no significant differences in the frequencies of bulbar-onset and limb-onset patients in
and
groups. ALS-frontotemporal dementia (FTD) was more common in
(17%) than in
(4%) patients, and of all patients with ALS-FTD, 70% were
.
These results provide further evidence for the short survival of
-associated ALS. A prominent role of the
and
variants was found in the Finnish population. An unusually high frequency of
was also found among patients with sporadic ALS. The enrichment of these 2 variants likely contributes to the high incidence of ALS in Finland.
Sprache
Englisch
Identifikatoren
ISSN: 2376-7839
eISSN: 2376-7839
DOI: 10.1212/NXG.0000000000000665
Titel-ID: cdi_proquest_miscellaneous_2640326898
Format
–
Weiterführende Literatur
Empfehlungen zum selben Thema automatisch vorgeschlagen von bX