https://scholars.lib.ntu.edu.tw/handle/123456789/519994
標題: | Genotype-phenotype correlations of adult-onset PLA2G6-associated Neurodegeneration: Case series and literature review | 作者: | Chu Y.-T. Lin H.-Y. PEI-LUNG CHEN CHIN-HSIEN LIN |
公開日期: | 2020 | 出版社: | BioMed Central Ltd. | 卷: | 20 | 期: | 1 | 來源出版物: | BMC Neurology | 摘要: | Background: Phospholipase A2 group VI (PLA2G6) mutations associated with neurodegeneration (PLAN) manifest as heterogeneous neurodegenerative disorders with variable ages of onset. The genotype-phenotype correlation is not well-established. We aim to describe three adult patients with PLAN and combined these data with results from previous studies to elucidate adult-onset PLA2G6 phenotype-genotype correlations. Case presentations: The first index patient presented with dystonia-parkinsonism starting at age 31 years, accompanied by major depression and cognitive decline. Genetic analysis using targeted next generation sequencing (NGS) panel, Sanger sequencing, and segregation analyses revealed a compound heterozygous mutation, c.991G > T (p.D331Y)/c.1077G > A (M358IfsX), in PLA2G6. The other two patients had levodopa-responsive, early-onset parkinsonism, starting in their late twenties. Both patients had homozygous c.991G > T (p.D331Y) mutations in PLA2G6. Patient characteristics of our reported 3 cases were compared to those of 32 previously described (2008 to 2019) patients with adult-onset PLAN. Among the combined cohort of 35 patients with adult-onset PLAN, 14 had dystonia-parkinsonism, 17 had early-onset Parkinson's disease, 3 had hereditary spastic paraparesis, and one had ataxia. The c.991G > T (p. D331Y) mutation was almost exclusively found in Chinese patients, suggesting a common founder effect. All patients with homozygous p.D331Y mutations had levodopa-responsive, early-onset PD (100%); while other mutations mostly led to dystonia-parkinsonism, ataxia, spasticity, and combine psychiatric comorbidities. Conclusions: We showed that adult-onset PLAN could present as purely parkinsonism features, without brain iron accumulation, particularly patients with homozygous p.D331Y mutations. Compound heterozygous mutations, including heterozygous p.D331Y, produced heterogeneous phenotypes, without obvious levodopa responsiveness. ? 2020 The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85081976738&doi=10.1186%2fs12883-020-01684-6&partnerID=40&md5=b8703a7979ff3bd2b803ccdd38837cf2 https://scholars.lib.ntu.edu.tw/handle/123456789/519994 |
ISSN: | 1471-2377 | DOI: | 10.1186/s12883-020-01684-6 | SDG/關鍵字: | levodopa; phospholipase A2 group VI; levodopa; phospholipase A2 group VI; PLA2G6 protein, human; adult; Article; ataxia; case report; case study; Chinese; clinical article; clinical feature; cohort analysis; comorbidity; drug effect; drug response; dystonia; female; gene mutation; genetic association; genotype phenotype correlation; hereditary motor sensory neuropathy; heterozygosity; high throughput sequencing; homozygosity; human; major depression; male; mental deterioration; middle aged; nerve degeneration; onset age; parkinsonism; PLA2G6 gene; Sanger sequencing; segregation analysis; Asian continental ancestry group; genetic association study; genetics; mutation; neuroaxonal dystrophy; Parkinson disease; parkinsonism; phenotype; Adult; Asian Continental Ancestry Group; Cohort Studies; Female; Genetic Association Studies; Group VI Phospholipases A2; High-Throughput Nucleotide Sequencing; Humans; Levodopa; Male; Middle Aged; Mutation; Neuroaxonal Dystrophies; Parkinson Disease; Parkinsonian Disorders; Phenotype |
顯示於: | 醫學系 |
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