Biallelic mutation of
Journal
Neurology. Genetics
ISSN: 2376-7839
Titre abrégé: Neurol Genet
Pays: United States
ID NLM: 101671068
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
03
05
2019
accepted:
19
11
2019
entrez:
12
2
2020
pubmed:
12
2
2020
medline:
12
2
2020
Statut:
epublish
Résumé
To determine the genetic underpinnings of slowly progressive spinocerebellar ataxia, autosomal recessive (SCAR), we performed exome analysis and examined the relationship between clinical severity and functional change induced by the mutation. Homozygosity fingerprinting and exome sequencing were performed to identify causative mutations in 2 consanguineous families. We assessed the expression of D-bifunctional protein (DBP) and the amount of dimerized DBP in fibroblasts by immunoblot and quantitative reverse transcription PCR. The pathogenicity of the mutation was evaluated using the Combined Annotation-Dependent Depletion (CADD) scores; these results were compared with the scores of previously reported mutations. We identified a homozygous mutation as causative of middle age-onset SCAR: p.Ala175Thr, which is located in This is the report of middle age-onset DBP deficiency. Residual functional DBP caused relatively mild symptoms in the affected patients, i.e., slowly progressive ataxia and hearing loss. This study broadens the scope of DBP deficiency phenotypes and indicates that CADD scores may be used to estimate the severity of DBP deficiencies.
Identifiants
pubmed: 32042923
doi: 10.1212/NXG.0000000000000396
pii: NG2019010918
pmc: PMC6975179
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e396Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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