Novel stop-gain RNF170 variation detected in a Chinese family with adolescent-onset hereditary spastic paraplegia.
Clin Genet
; 103(1): 87-92, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36046950
ABSTRACT
Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disease characterized by progressive lower limb spasticity. Recent studies revealed that biallelic variants in RNF170 gene cause autosomal recessive complicated HSP with infancy onset. Here, we report an adolescent-onset HSP patient from a consanguineous Chinese family, with lower extremity stiffness, spastic gait, and unstable straight-line walking as the main manifestations. Whole-exome sequencing identifies a novel RNF170 mutation c.190C>T (p.R64*), which co-segregates with the disease in this pedigree. Functional analysis, including quantitative real-time PCR (RT-qPCR) and Western blot, indicates that both the mRNA and protein levels of mutant RNF170 are significantly reduced, which confirms the loss-of-function mechanism. Our study expands the spectrum of RNF170-associated HSP, while the RNF170 protein-involved degradation of the inositol 1,4,5-trisphosphate receptor in neurodegenerative motor neuron disorders deserves further investigation.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Paraplegia Espástica Hereditária
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Doenças Neurodegenerativas
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Ubiquitina-Proteína Ligases
Limite:
Adolescent
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article