A heterozygous mutation in the CCDC88C gene likely causes early-onset pure hereditary spastic paraplegia: a case report.
BMC Neurol
; 21(1): 78, 2021 Feb 18.
Article
em En
| MEDLINE
| ID: mdl-33602173
ABSTRACT
BACKGROUND:
CCDC88C is a ubiquitously expressed protein with multiple functions, including roles in cell polarity and the development of dendrites in the nervous system. Bi-allelic mutations in the CCDC88C gene cause autosomal recessive congenital hydrocephalus (OMIM #236600). Studies recently linked heterozygous mutations in CCDC88C to the development of the late-onset spinocerebellar ataxia type 40 (OMIM #616053). CASE PRESENTATION A 48-year-old Sudanese female presented with pure early onset hereditary spastic paraplegia. Exome sequencing, in-silico analysis, and Sanger sequencing identified the heterozygous NM_001080414.4c.1993G > A (p.E665K) variant in CCDC88C as a potential cause of her illness. To explore the pathogenicity of the NM_001080414.4c.1993G > A (p.E665K) variant, we expressed it in human embryonic kidney 293 cells and assessed its effects on apoptosis. In our experiment, NM_001080414.4c.1993G > A (p.E665K) induced JNK hyper-phosphorylation and enhanced apoptosis. In contrast to previous reports, our patient developed neurological symptoms in early childhood and showed neither features of cerebellar ataxia, extrapyramidal signs, nor evidence of intellectual involvement.CONCLUSION:
We, herein, heighlighted the possibility of extending the phenotype associated with variants in CCDC88C to include early-onset pure hereditary spastic paraplegia.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Paraplegia Espástica Hereditária
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas dos Microfilamentos
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Female
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Humans
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Middle aged
Idioma:
En
Revista:
BMC Neurol
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Sudão