A New Case Series Suggests That SCA48 (ATX/STUB1) Is Primarily a Monogenic Disorder.
ataxia
genetics
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
07 Jul 2024
07 Jul 2024
Historique:
revised:
27
05
2024
received:
19
04
2024
accepted:
17
06
2024
medline:
8
7
2024
pubmed:
8
7
2024
entrez:
8
7
2024
Statut:
aheadofprint
Résumé
Monoallelic, pathogenic STUB1 variants cause autosomal dominant cerebellar ataxia (ATX-STUB1/SCA48). Recently, a genetic interaction between STUB1 variants and intermediate or high-normal CAG/CAA repeats in TBP was suggested, indicating digenic inheritance or a disease-modifying role for TBP expansions. To determine the presence and impact of intermediate or high-normal TBP expansions in ataxic patients with heterozygous STUB1 variants. We describe 21 patients with ataxia carrying a heterozygous STUB1 variant and determined TBP repeat length. A total of 15 of 21 patients (71%) carried a normal TBP SCA48 is predominantly a monogenic disorder, because most patients carried an isolated, heterozygous STUB1 variant and presented with the typical combined phenotype of ataxia and cognitive dysfunction. Still, co-occurrence of TBP
Sections du résumé
BACKGROUND
BACKGROUND
Monoallelic, pathogenic STUB1 variants cause autosomal dominant cerebellar ataxia (ATX-STUB1/SCA48). Recently, a genetic interaction between STUB1 variants and intermediate or high-normal CAG/CAA repeats in TBP was suggested, indicating digenic inheritance or a disease-modifying role for TBP expansions.
OBJECTIVE
OBJECTIVE
To determine the presence and impact of intermediate or high-normal TBP expansions in ataxic patients with heterozygous STUB1 variants.
METHODS
METHODS
We describe 21 patients with ataxia carrying a heterozygous STUB1 variant and determined TBP repeat length.
RESULTS
RESULTS
A total of 15 of 21 patients (71%) carried a normal TBP
CONCLUSIONS
CONCLUSIONS
SCA48 is predominantly a monogenic disorder, because most patients carried an isolated, heterozygous STUB1 variant and presented with the typical combined phenotype of ataxia and cognitive dysfunction. Still, co-occurrence of TBP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Références
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