Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Type of study
Language
Publication year range
1.
J Med Genet ; 57(12): 835-842, 2020 12.
Article in English | MEDLINE | ID: mdl-32179706

ABSTRACT

BACKGROUND: UBA5 is the activating enzyme of UFM1 in the ufmylation post-translational modification system. Different neurological phenotypes have been associated with UBA5 pathogenic variants including epilepsy, intellectual disability, movement disorders and ataxia. METHODS AND RESULTS: We describe a large multigenerational consanguineous family presenting with a severe congenital neuropathy causing early death in infancy. Whole exome sequencing and linkage analysis identified a novel homozygous UBA5 NM_024818.3 c.31C>T (p.Arg11Trp) mutation. Protein expression assays in mouse tissue showed similar levels of UBA5 in peripheral nerves to the central nervous system. CRISPR-Cas9 edited HEK (human embrionic kidney) cells homozygous for the UBA5 p.Arg11Trp mutation showed reduced levels of UBA5 protein compared with the wild-type. The mutant p.Arg11Trp UBA5 protein shows reduced ability to activate UFM1. CONCLUSION: This report expands the phenotypical spectrum of UBA5 mutations to include fatal peripheral neuropathy.


Subject(s)
CRISPR-Cas Systems/genetics , Intellectual Disability/genetics , Nervous System Malformations/genetics , Proteins/genetics , Ubiquitin-Activating Enzymes/genetics , Ataxia/genetics , Ataxia/pathology , Central Nervous System/metabolism , Central Nervous System/pathology , Consanguinity , Epilepsy/genetics , Epilepsy/pathology , Female , Gene Expression Regulation/genetics , Genetic Linkage , HEK293 Cells , Homozygote , Humans , Infant , Intellectual Disability/pathology , Male , Movement Disorders/genetics , Movement Disorders/pathology , Mutation/genetics , Nervous System Malformations/pathology , Pedigree , Peripheral Nerves/metabolism , Peripheral Nerves/pathology
SELECTION OF CITATIONS
SEARCH DETAIL
...