| Autor: |
Shih‐Yu Fang, Ying‐Tsen Chou, Kuo‐Chou Hsu, Shao‐Lun Hsu, Kai‐Wei Yu, Yu‐Shuen Tsai, Yi‐Chu Liao, Pei‐Chien Tsai, Yi‐Chung Lee |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Annals of clinical and translational neurologyReferences. |
| ISSN: |
2328-9503 |
| Popis: |
NIPA1 mutations have been implicated in hereditary spastic paraplegia (HSP) as the cause of spastic paraplegia type 6 (SPG6). The aim of this study was to investigate the clinical and genetic features of SPG6 in a Taiwanese HSP cohort.We screened 242 unrelated Taiwanese patients with HSP for NIPA1 mutations. The clinical features of patients with a NIPA1 mutation were analyzed. Minigene-based splicing assay, RT-PCR analysis on the patients' RNA, and cell-based protein expression study were utilized to assess the effects of the mutations on splicing and protein expression.Two patients were identified to carry a different heterozygous NIPA1 mutation. The two mutations, c.316GA and c.316GC, are located in the 3' end of NIPA1 exon 3 near the exon-intron boundary and putatively lead to the same amino acid substitution, p.G106R. The patient harboring NIPA1 c.316GA manifested spastic paraplegia, epilepsy and schizophrenia since age 17 years, whereas the individual carrying NIPA1 c.316GC had pure HSP since age 12 years. We reviewed literature and found that epilepsy was present in multiple individuals with NIPA1 c.316GA but none with NIPA1 c.316GC. Functional studies demonstrated that both mutations did not affect splicing, but only the c.316GA mutation was associated with a significantly reduced NIPA1 protein expression.SPG6 accounted for 0.8% of HSP cases in the Taiwanese cohort. The NIPA1 c.316GA and c.316GC mutations are associated with adolescent-onset complex and pure form HSP, respectively. The different effects on protein expression of the two mutations may be associated with their phenotypic discrepancy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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