PLA2G6-Associated Neurodegeneration (PLAN): Review of Clinical Phenotypes and Genotypes

Guo, Yu-pei; Tang, Beisha; Guo, Jifeng

doi:10.3389/fneur.2018.01100

Cited by 73 publications

(81 citation statements)

References 100 publications

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“…Including our three patients, we analyzed data for 35 patients. The clinical characteristics and genetic findings are summarized in Table 1 [1][2][3]. The mean age of onset was 26.3 ± 8.6 years.…”

Section: Systematic Review Of Previous Reports Of Patients With Planmentioning

confidence: 99%

“…The crystal structure of iPLA2β is complex, and the different mutation sites are disparately located on the enzyme [1]. Different mutation sites in the different domains of iPLA2β can lead to different changes in enzymatic activities; however, iPLA2β enzyme activity is the crucial factor that affects the clinical phenotypes of PLAN [33].…”

Section: Comparison Of Patients With Different Plan-related Genotypesmentioning

confidence: 99%

“…PLA2G6-associated neurodegeneration (PLAN) is a heterogeneous group of neurodegenerative disorders that result from mutations in the phospholipase A2 group VI gene (PLA2G6) [1,2]. The PLA2G6 gene encodes a group of VIA calcium-independent phospholipase A2 proteins.…”

Section: Introductionmentioning

confidence: 99%

“…The PLA2G6 gene encodes a group of VIA calcium-independent phospholipase A2 proteins. Phospholipase A2 is an enzyme involved in phospholipid metabolism, and it is essential for maintaining cell membrane integrity [1,2]. PLAN can be classified into four subtypes, based on onset age, including: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia-parkinsonism, and autosomal recessive early-onset parkinsonism (known as PARK14) [3].…”

Section: Introductionmentioning

confidence: 99%

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Genotype-phenotype correlations of adult-onset PLA2G6-associated Neurodegeneration: case series and literature review

et al. 2020

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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.

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Section: Systematic Review Of Previous Reports Of Patients With Planmentioning

confidence: 99%

Section: Comparison Of Patients With Different Plan-related Genotypesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genotype-phenotype correlations of adult-onset PLA2G6-associated Neurodegeneration: case series and literature review

et al. 2020

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“…In contrast, excessive iron deposition in the GP is seen in only up to half of PLAN cases ( 7 , 55 ). Disproportionate cerebellar atrophy and iron deposition can be absent in adult-onset PLAN ( 56 , 59 , 60 ), where there may be only frontally predominant atrophy ( 61 ) and MRI may even appear normal ( 56 ).…”

Section: Non-iron and Extrapallidal Abnormalitiesmentioning

confidence: 99%

Brain MRI Pattern Recognition in Neurodegeneration With Brain Iron Accumulation

et al. 2020

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Most neurodegeneration with brain iron accumulation (NBIA) disorders can be distinguished by identifying characteristic changes on magnetic resonance imaging (MRI) in combination with clinical findings. However, a significant number of patients with an NBIA disorder confirmed by genetic testing have MRI features that are atypical for their specific disease. The appearance of specific MRI patterns depends on the stage of the disease and the patient's age at evaluation. MRI interpretation can be challenging because of heterogeneously acquired MRI datasets, individual interpreter bias, and lack of quantitative data. Therefore, optimal acquisition and interpretation of MRI data are needed to better define MRI phenotypes in NBIA disorders. The stepwise approach outlined here may help to identify NBIA disorders and delineate the natural course of MRI-identified changes.

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Novel insertion mutation in the PLA2G6 gene in an Iranian family with infantile neuroaxonal dystrophy

Rostampour

Zolfaghari

Gholami

2022

Clinical Laboratory Analysis

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Background: Infantile neuroaxonal dystrophy is an autosomal recessive neurological disorder. Individuals with infantile neuroaxonal dystrophy experience progressive loss of vision, mental skills and muscular control, and other variable clinical signs. Pathogenic variants in the PLA2G6 gene, encoding phospholipase A2, are recognized to be the fundamental reason for infantile neuroaxonal dystrophy. This study aimed to detect pathogenic variant in a consanguine Iranian family with infantile neuroaxonal dystrophy. Methods: The mutation screening was done by whole exome sequencing followed by direct Sanger sequencing. Results: We identified a homozygous insertion mutation, NM_003560: c.1548_1549insCG (p.G517Rfs*29) in exon 10 of PLA2G6 in the patient. The parents were heterozygous for variant. Conclusions: Because of the clinical heterogeneity and rarity of infantile neuroaxonal dystrophy, whole exome sequencing is critical to confirm the diagnosis and is an excellent tool for INAD management.

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PLA2G6-Associated Neurodegeneration (PLAN): Review of Clinical Phenotypes and Genotypes

Cited by 73 publications

References 100 publications

Genotype-phenotype correlations of adult-onset PLA2G6-associated Neurodegeneration: case series and literature review

Genotype-phenotype correlations of adult-onset PLA2G6-associated Neurodegeneration: case series and literature review

Brain MRI Pattern Recognition in Neurodegeneration With Brain Iron Accumulation

Novel insertion mutation in the PLA2G6 gene in an Iranian family with infantile neuroaxonal dystrophy

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