Frequency of spinocerebellar ataxia mutations in patients with multiple system atrophy.
Genetics
Multiple system atrophy
Spinocerebellar ataxia
Journal
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
ISSN: 1619-1560
Titre abrégé: Clin Auton Res
Pays: Germany
ID NLM: 9106549
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
21
09
2020
accepted:
18
12
2020
pubmed:
28
1
2021
medline:
25
11
2021
entrez:
27
1
2021
Statut:
ppublish
Résumé
Investigate single nucleotide variants and short tandem repeats in 39 genes related to spinocerebellar ataxia in clinical and pathologically defined cohorts of multiple system atrophy. Exome sequencing was conducted in 28 clinical multiple system atrophy patients to identify single nucleotide variants in spinocerebellar ataxia-related genes. Novel variants were validated in two independent disease cohorts: 86 clinically diagnosed multiple system atrophy patients and 166 pathological multiple system atrophy cases. Expanded repeat alleles in spinocerebellar ataxia genes were evaluated in 36 clinically diagnosed multiple system atrophy patients, and CAG/CAA repeats in TATA-Box Binding Protein (TBP, causative of SCA17) were screened in 216 clinical and pathological multiple system atrophy patients and 346 controls. No known pathogenic spinocerebellar ataxia single nucleotide variants or pathogenic range expanded repeat alleles of ATXN1, ATXN2, ATXN3, CACNA1A, AXTN7, ATXN8OS, ATXN10, PPP2R2B, and TBP were detected in any clinical multiple system atrophy patients. However, four novel variants were identified in four spinocerebellar ataxia-related genes across three multiple system atrophy patients. Additionally, four multiple system atrophy patients (1.6%) and one control (0.3%) carried an intermediate length 41 TBP CAG/CAA repeat allele (OR = 4.11, P = 0.21). There was a significant association between the occurrence of a repeat length of longer alleles (> 38 repeats) and an increased risk of multiple system atrophy (OR = 1.64, P = 0.03). Occurrence of TBP CAG/CAA repeat length of longer alleles (> 38 repeats) is significantly associated with increased multiple system atrophy risk. This discovery warrants further investigation and supports a possible genetic overlap of multiple system atrophy with SCA17.
Identifiants
pubmed: 33502644
doi: 10.1007/s10286-020-00759-1
pii: 10.1007/s10286-020-00759-1
pmc: PMC9302534
mid: NIHMS1821420
doi:
Substances chimiques
ATXN10 protein, human
0
Ataxin-10
0
TATA-Box Binding Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
117-125Subventions
Organisme : FDA HHS
ID : R01 FD004789
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS078086
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS092625
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS065736
Pays : United States
Organisme : NINDS NIH HHS
ID : P50 NS072187
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS110435
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS044233
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS100693
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003949
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG045390
Pays : United States
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