Download PDF
Brief Communication  |  Open Access  |  30 May 2023

Identification of PLA2G6 variants in a Chinese patient with Parkinson's disease

Views: 1045 |  Downloads: 191 |  Cited:  0
Ageing Neur Dis 2023;3:9.
10.20517/and.2023.06 |  © The Author(s) 2023.
Author Information
Article Notes
Cite This Article


Parkinson’s disease (PD) is a clinical syndrome and a heterogeneous group of neurodegenerative conditions with variable pathologies and clinical sub-entities, characterized by motor symptoms and non-motor features. PD represents an outcome of the combination of genes and other risk or protective factors. Patients with variants in the phospholipase A2 group VI gene (PLA2G6) can present complex Parkinsonian phenotypes. This study reported a PD patient with typical motor symptoms of PD, including bradykinesia, gait disturbance, rigidity, and rest tremor, who also suffered from nocturia, constipation, and sleeping problems. Two PLA2G6 variants, c.402C>T and c.2327_2328del, were identified in the patient by whole exome sequencing followed by Sanger sequencing. The transition c.402C>T was predicted to generate an alternative acceptor splice site, though the minigene splicing assay showed negative in vitro outcomes. The novel variant c.2327_2328del was predicted to result in a truncated protein. These two variants may be pathogenic in PD or increase the susceptibility to PD individually or collaboratively. This discovery may enrich the genetic landscape of PLA2G6-associated PD and confirm the notion of prioritizing whole exome sequencing analysis in patients with PD.


Parkinson’s disease, genetics, PLA2G6, variants


Parkinson’s disease (PD) is a recognizable clinical syndrome and a heterogeneous group of neurodegenerative conditions with variable pathologies and distinct clinical sub-entities in the disease spectrum[1,2]. The diagnosis of PD is based on clinical manifestations characterized by three primary motor features: bradykinesia with either rest tremor or rigidity, or both[3]. The motor symptoms of PD include bradykinesia, changes in posture and gait, dysphagia, and dysarthria[2,3]. Non-motor features of PD usually precede motor symptoms, including hyposmia, orthostatic hypotension, constipation, urinary dysfunction, cognitive/psychiatric problems, pain, and sleep disturbances[1,4]. The pathological characteristic of PD is the accumulation of α-synuclein with dopaminergic neuronal loss in the substantia nigra as well as other brain areas[2,4]. PD represents an outcome of the combination of genes and other risk or protective factors such as aging, environmental toxins (pesticide and heavy metal exposure), and behavioral factors (coffee intake, chocolate consumption, or cigarette smoking)[5,6]. Several pathophysiologic mechanisms intersecting with each other contribute to the disease pathogenesis, including α-synuclein accumulation, mitochondrial dysfunction, neuroinflammation triggered by risk factors exposure, oxidative stress, and autophagy dysfunction[5-7].

The genetic architecture of PD is extremely complicated, with at least 20 Mendelian inherited causative genes and over 100 genetic risk loci[6,8]. For monogenic forms that affect approximately 5%-10% of PD patients, 11 autosomal dominant genes (the synuclein alpha gene, SNCA; the ubiquitin C-terminal hydrolase L1 gene, UCHL1; the leucine rich repeat kinase 2 gene, LRRK2; the GRB10 interacting GYF protein 2 gene, GIGYF2; the HtrA serine peptidase 2 gene, HTRA2; the VPS35 retromer complex component gene, VPS35; the eukaryotic translation initiation factor 4 gamma 1 gene, EIF4G1; the transmembrane protein 230 gene, TMEM230; the coiled-coil-helix-coiled-coil-helix domain containing 2 gene, CHCHD2; the RIC3 acetylcholine receptor chaperone gene, RIC3; the prosaposin gene, PSAP) and 9 autosomal recessive genes (the parkin RBR E3 ubiquitin protein ligase gene, PRKN; the PTEN induced putative kinase 1 gene, PINK1; the Parkinsonism associated deglycase gene, PARK7; the ATPase 13A2 gene, ATP13A2; the phospholipase A2 group VI gene, PLA2G6; the F-box protein 7 gene, FBXO7; the DnaJ heat shock protein family (Hsp40) member C6 gene, DNAJC6; the synaptojanin 1 gene, SYNJ1; the vacuolar protein sorting 13 homolog C gene, VPS13C) have been reported[9,10]. Despite excitement about increasing monogenic PD cases defined on a molecular basis, only several genes are well-established, responsible for autosomal dominant (SNCA, LRRK2, and VPS35) or recessive (PRKN, PINK1, and PARK7) forms of the disease[10,11]. Moreover, patients with variants in ATP13A2, the dynactin subunit 1 gene (DCTN1), DNAJC6, FBXO7, PLA2G6, and SYNJ1 can present with atypical or complex parkinsonian phenotypes[4,11]. The PLA2G6 gene (OMIM 603604) was initially reported to be responsible for Parkinson’s disease 14 (PARK14, OMIM 612953) in 2009[12]. Since then, over 54 different variants have been identified in PLA2G6-related PD, including missense and nonsense variants, in-frame deletions, splicing variants, and frameshift changes[13].

In the present study, we described a Han Chinese patient with clinical manifestations compatible with the PARK14 phenotype, in whom two PLA2G6 variants (NM_003560.4), c.402C>T and c.2327_2328del, were detected.


One subject (II:1, Figure 1A) with PD from Yongzhou, Hunan, China, was included in the present study. The patient was born to non-consanguineous parents, and there was no history of similar neurological signs in her parents (I:1 and I:2, died, Figure 1A). Neurological examination and brain magnetic resonance imaging were undertaken on the patient. Clinical data and peripheral blood sample were acquired from the patient after obtaining written informed consent for genetic analysis. This study was approved by the Institutional Review Board of the Third Xiangya Hospital, Central South University, Changsha, China, and all procedures were performed in accordance with the ethical standards of the Declaration of Helsinki.

Identification of <i>PLA2G6</i> variants in a Chinese patient with Parkinson's disease

Figure 1. (A) Pedigree of a Chinese family with Parkinson’s disease. A square indicates a male and circles indicate females. The fully shaded symbol indicates the affected individual and the empty symbols indicate unaffected members. Slashed symbols represent deceased members. (B, C) The sequencing for the PLA2G6 variants, c.402C>T and c.2327_2328del, in the individual (II:1) with Parkinson’s disease. (D) Cartoon models of the wild-type (left) and mutated (right) PLA2G6 proteins shown by PyMOL. The segments of wild-type (WT) PLA2G6 protein (residues 776-806) and mutated (MT) PLA2G6 protein caused by the variant c.2327_2328del [p.(Thr776Serfs*15], residues 776-789) are marked in the cartoon models, and the corresponding sequences are shown in the bottom. PLA2G6: phospholipase A2 group VI gene

Whole exome sequencing (WES) was performed using genomic DNA obtained from a peripheral blood sample according to a previously reported saturated phenol-chloroform extraction method[14]. The sequencing was performed at BGI-Shenzhen (Shenzhen, China). In brief, the library was prepared using the DNA nanoballs and combinatorial probe-anchor synthesis technology, and the sequencing was fulfilled in the DNBSEQ platform. DNBSEQ base-calling software was used to transform raw image files derived from sequencing into raw reads.

Generated clean data via raw data filtration by SOAPnuke (v2.1.0) were aligned to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (v0.7.17). The sequencing data alignment, base quality value correction, and variant calling were performed using Genome Analysis Toolkit (GATK, v4.1.4.1). The GATK MarkDuplicates tool was used to mark the duplicate reads. After the removal of the duplicate reads, base quality score recalibration was performed by GATK BaseRecalibrator and GATK ApplyBQSR. GATK HaplotypeCaller was used for single nucleotide polymorphisms and insertions/deletions detection. The variants were filtered out through GATK SelectVariants and GATK VariantFiltration, and annotated using the Annodb software, with reference to databases including the Single Nucleotide Polymorphism database, the 1000 Genomes Project, Exome Sequencing Project 6500, and the BGI in-house exome database. Variants whose minor allele frequency ≥ 0.01 were filtered out. The candidate variants were checked against ClinVar, the Human Gene Mutation Database, and PubMed. The global population of the Genome Aggregation Database and the Exome Aggregation Consortium database were surveyed to search for the variant frequency in the population. MutationTaster, MutationAssessor, Sorting Intolerant from Tolerant, and Polymorphism Phenotyping v2 were utilized to predict the pathogenicity of candidate variants. Synonymous variants and variants in the potential donor or acceptor splice site were predicted by Berkeley Drosophila Genome Project (BDGP) Splice Site Prediction by Neural Network tool ( The consensus approach meta-server from Zhang Lab ( and PyMOL software (v2.6.0a0, Schrödinger, LLC, Portland, U.S.A.) were used to predict and perform the structural comparison of the wild-type and mutated proteins[15,16].

Primers for Sanger sequencing were designed by Primer3 (v4.1.0,, including PLA2G6-c.402C>T-F: 5’-CCCTTCTATGAGAGCTCCCC-3’, and PLA2G6-c.402C>T-R: 5’-CCACACAAGCAGGTACACAC-3’, PLA2G6-c.2327_2328del-F: 5’-CCTGAGCATCCTAGGGTGAC-3’, and PLA2G6-c.2327_2328del-R: 5’- GGGCTGAATGGACGAGGT-3’. Polymerase chain reaction (PCR) amplification and Sanger sequencing were used to verify the detected variants. Chromas software (v2.6.6) was used to align the sequencing results with the gene reference sequence.

The minigene regions encompassing whole exons 2-4 and partial introns 2-4 of the PLA2G6 gene (NG_007094.3, NM_003560.4: c.402C>T) from genomic DNA of controls were PCR-amplified using seamless cloning strategies with two pairs of primers carrying restriction sites for BamHI/XhoI. The following were the paired primer sequences, respectively: PLA2G6-AF: 5’-AAGCTTGGTACCGAGCTCGGATCCACAGAGGGGGAAGACGGTGGGGCCT-3’ and PLA2G6-AR: 5’-TTACAGGCATAGAGCCAGGGCTAAAGGTTCTCCCCATG-3’, PLA2G6-BF: 5’-CCCTGGCTCTATGCCTGTAATCCCAGCTACTCAGGAAC-3’ and PLA2G6-BR: 5’-TTAAACGGGCCCTCTAGACTCGAGCTGCAGCACCTGAGAATTGTCACCCT-3’. The segments including the variant sequence were obtained with mutagenesis primers of PLA2G6-MT-F (5’-CGCGAGTGtTTCCATCACAGCCGTATCATCAG-3’) and PLA2G6-MT-R (5’-TGATGGAAaCACTCGCGGATCCCTAGCTCCAC-3’). PCR products were subcloned into pMini-CopGFP vector (Beijing Hitrobio Biotechnology Co., Ltd., Beijing, China) using ClonExpress II One Step Cloning Kit (Vazyme Biotech Co., Ltd., Nanjing, China). The minigene expression plasmids were confirmed by Sanger sequencing.

For minigene assay, human embryonic kidney 293T cells (Beijing Hitrobio Biotechnology Co., Ltd., Beijing, China) were cultured to 50%-60% confluency of Dulbecco’s Modified Eagle Medium (ThermoFisher Scientific, China), supplemented with 10% fetal bovine serum (PAN-Biotech Ltd, Aidenbach, Germany) in 35-mm cell culture dishes at 37°C and 5% CO2 atmosphere. Transfection of wild-type and mutated minigene constructs was performed using the LipofectamineTM 2000 Transfection Reagent (ThermoFisher Scientific, China). The constructs were transiently transfected into cultured human embryonic kidney 293T cells. At 48-hour post-transfection, reverse transcription-PCR analysis using MiniRT-F (5’-GGCTAACTAGAGAACCCACTGCTTA-3’) and PLA2G6-RT-R (5’-CTGCAGCACCTGAGAATTGTCAC-3’) primers, and Sanger sequencing was performed to compare the splicing pattern of the transcripts generated from both constructs.


The patient (II:1, Figure 1A), a 67-year-old female, claimed to be in good health until age 65 years when she developed bradykinesia and left leg clumsiness, and later developed stiffness of the upper limbs, decreased arm swing, rest tremor in the upper limbs, and constipation. At the age of 67 years, she presented marked foot-dragging, gait disturbance, rigidity, and rest tremor. She also suffered from nocturia, significant constipation, and sleeping problems. No affective symptom was reported. Her examination at age 67 showed a masked face, speech dysfluency, hypophonia, impaired postural reflexes, decreased blink, negative Brudzinski, negative Kerning, and negative Babinski. There was bradykinesia on chewing and swallowing, and she manifested stiffness and clumsiness of movements. Physical examination revealed normal muscle strength, normal plantar responses, and increased muscle tone in all limbs, with the right side more severely affected. A sensory system, pyramidal and cerebellar examination were unremarkable. The brain magnetic resonance imaging revealed that the brain was scattered with ischemic foci. Levodopa was prescribed at a dose of 125 mg two times a day, and the response was quite good without levodopa-induced dyskinesia. The results of a detailed clinical examination of the patient are shown in Table 1.

Table 1

Clinical features of our patient with PLA2G6 c.402C>T and c.2327_2328del variants

ItemThe patient (II:1)
Age at examination67 years
Age at onset65 years
Family historyNo
Consanguineous marriageNo
Symptoms at onsetFoot dragging, gait disturbance, decreased arm swing, and left leg clumsiness
Motor features
Rest tremor (Distribution)Yes (Left/right hand/arm)
Gait disturbanceYes
Imbalance/impaired postural reflexesYes
DysarthriaYes (Hypophonia and speech dysfluency)
Decreased blinkYes
Levodopa-induced dyskinesiaNo
Muscle toneIncreased
Muscle strengthNormal
Sensory abnormalitiesNo
Plantar reflexNormal
Babinski signNo
Meningeal irritation signsNo
Cognitive declineNo
Psychiatric dysfunctionsNo
Sleeping disturbancesYes (Insomnia)
Autonomic involvementYes (Nocturia and constipation)
Cerebellar signsNo
Magnetic resonance imagingScattered ischemic foci in the brain
TreatmentLevodopa 250 mg/day

WES generated 90 million raw reads and approximately 86.23 million clean reads after filtration. The total effective bases were 11,830.90 Mb and 99.97% were aligned to the human reference sequence. Effective bases on target were 7,133.59 Mb with an average sequencing depth of 117.99×, and the target coverage at 20× was 97.95%. A total of 130,131 single nucleotide polymorphisms and 24,837 insertions/deletions were identified, including synonymous, missense variants, nonsense variants, splicing variants, in-frame variants, and frameshift variants. After a comprehensive analysis, candidate disease-causing PLA2G6 variants c.402C>T and c.2327_2328del were identified in the patient. Both PLA2G6 variants were confirmed with Sanger sequencing [Figures 1B and C].

The synonymous variant, c.402C>T, p.(Cys134=), has been recorded in the Single Nucleotide Polymorphism database (rs200522242) with a low frequency in the Genome Aggregation Database (0.00011) and the Exome Aggregation Consortium database (0.00023), while it has not been reported in ClinVar, the Human Gene Mutation Database, or the literature. BDGP splice site prediction tool showed the transition c.402C>T may generate a new acceptor splice site. Electrophoresis analysis revealed that the tested mutated minigene construct produced two different transcripts, consistent with the wild-type construct. The c.2327_2328del variant, predicted to cause a frameshift leading to a premature truncation, p.(Thr776Serfs*15), was unreported in searched databases. A structural illustration of the wild-type and mutated PLA2G6 proteins was generated [Figure 1D].


In the current study, two variants of the PLA2G6 gene, c.402C>T and c.2327_2328del, were identified in a Chinese patient with PD. The PLA2G6 gene, which encodes a calcium-independent group VI phospholipase A2β (iPLA2β), resides on chromosome 22q13.1 and contains 17 exons for the VIA-1 transcript (NM_003560.4)[17]. Except for PD, variants in the PLA2G6 gene were also associated with other autosomal recessive neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation 2B, and hereditary spastic paraplegia[18]. Pathogenic PLA2G6 variants may take distinct effects on iPLA2β enzymatic activity, regulation, or interactions via various loss-of-function mechanisms, and therefore affect the clinical phenotypes of PLA2G6-associated neurodegeneration (PLAN)[13,19]. By merging data from the literature, PLAN cases harboring homozygous PLA2G6 variants were summarized, and it showed the consistent genotype-phenotype correlation of the disease[20]. Most reported patients with PLA2G6-parkinsonism carry two missense variants, suggesting there is a trend wherein PARK14 is associated with the presence of missense variants.

The full length of iPLA2β protein encompasses seven ankyrin repeats, a highly conserved patatin-like phospholipase domain, a proline-rich motif, a glycine-rich nucleotide binding motif, a serine lipase motif, and a proposed C-terminal Ca2+-dependent calmodulin-binding domain[21,22]. However, neither of the two variants identified in this study was located in the known motif or domain. The iPLA2β protein exerts a critical effect on maintaining membrane homeostasis by phospholipid remodeling and generating lipid second messengers. It also involves insulin secretion, Ca2+ signaling, mitochondrial dynamics, cellular proliferation and migration, and autophagy[13,23]. Multiple isoforms of iPLA2β caused by alternative splicing are associated with tissue-specific and dynamic cellular localization, different catalytic activities, and likely cellular function[24,25]. Research showed that loss of PLA2G6 impaired store-operated Ca2+ signaling, which led to premature loss of dopaminergic neurons via autophagy and other pathological processes, implicating the pivotal role in neurodegeneration[26,27]. Mitochondrial dysfunction that occurs early in PLAN may lead to loss of normal iPLA2β function, cell death, and neurodegeneration[28].

It is speculated that alterations of iPLA2β enzyme activity may arise from distinct PLA2G6 variants in iPLA2β domains and the number of affected alleles in PD patients. The heterozygous or homozygous PLA2G6 variant may give rise to a partial or significant decrease in its enzymatic activity[29]. No PLA2G6-parkinsonism variants hitherto have been reported to affect the primary structure of iPLA2β that impairs its enzyme activity[13]. In vitro, experiments showed PLA2G6 missense variants (p.Asp331Tyr, p.Gly517Cys, p.Thr572Ile, p.Arg632Trp, p.Leu656Val, p.Asn659Ser, and p.Leu693Val) and frameshift variant (p.Leu598Serfs*68) associated with PD could decrease iPLA2β phospholipase activity[30-32]. Some PLA2G6 variants associated with PD, including p.Arg632Trp and p.Arg747Trp, were shown not to impair the catalytic activity, but they may be involved in substrate recognition or other regulatory mechanisms of iPLA2β[33,34]. The role of p.Arg741Gln was controversial, for the normal catalytic activity of recombinant iPLA2β proteins was reported, while another study showed impairment of the iPLA2β ability to exert a neuroprotective effect by maintaining mitochondrial function[31,33].

Synonymous variant c.1077G>A in the PLA2G6 gene was reported to have key functions in activating a cryptic splice site leading to aberrant splicing[35]. Our synonymous variant c.402C>T was presumed to give rise to alter splice acceptor by the BDGP splice site prediction tool. However, the minigene assay showed wild-type and mutated (c.402C>T) PLA2G6 produced the same splicing pattern, indicating that PLA2G6 c.402C>T variant did not affect mRNA processing in vitro. The negative in vitro outcomes cannot entirely exclude the possibility of splicing alterations in affected tissues, and the plausible explanations include the cell- and tissue-specific technical issues, the methods used to characterize transcripts, and so on.

The c.2327_2328del variant of PLA2G6 corresponding to a frameshift variant was considered as the potential pathogenic variant in the patient. The 2-bp deletion in the exon 17 of the PLA2G6 gene is located in an undetermined functional region and might contribute to prematurely terminated PLA2G6 mRNA and premature truncation of iPLA2β enzyme, p.(Thr776Serfs*15). We surmised that the c.2327_2328del variant may result in a truncated protein or exert a deleterious effect via nonsense-mediated decay leading to mRNA degradation, which probably plays a pathogenic role in PD combined with the c.402C>T variant, or it only increases the susceptibility to PD under the circumstances in which the c.402C>T variant may not affect natural PLA2G6 protein function, or these two variants in cis may individually or collaboratively increase the PD susceptibility, implicating a haploinsufficiency mechanism.

Considering the high heterogeneity of PD, the unbiased approach of WES, along with Sanger sequencing, is effective in identifying the underlying genetic cause. Current treatments for PLA2G6-related PD patients are symptomatic relief, and primarily dopaminergic agents are geared towards alleviating parkinsonism and dystonia[1]. Thus, future studies to identify more PLA2G6-related PD patients and develop newer therapy strategies or preventive interventions based on reliable biomarkers are warranted.

In conclusion, we identified two PLA2G6 variants in this study, which may enrich the genetic landscape of PLA2G6-associated parkinsonism and confirm the notion of prioritizing WES analysis in patients with PD. Further functional studies in site-specific genetic deficiency animal models are needed to assess the role of PLA2G6 variants in PD, unravel the molecular mechanism in PLA2G6 variants, and develop more rational drug treatments.


Authors’ contributions

Formal analysis: Deng X, Li H, Deng H, Yuan L

Investigation: Deng X, Zheng W, Yang Y, Yang Z, Song Z, Wang J, Deng H, Yuan L

Writing & original draft: Deng X, Zheng W

Writing & review and editing: Deng X, Deng H, Yuan L

Availability of data and materials

All data generated during the study are available from the corresponding author upon reasonable request.

Financial support and sponsorship

This work was supported by the National Natural Science Foundation of China (No. 81873686), Scientific Key Research Project of Health Commission of Hunan Province (No. A202303018385), Natural Science Foundation of Hunan Province (No. 2020JJ3057), the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University (No. YX202109), and Hunan Province-level College Students’ Innovative Training Plan Program (No. S2022105330510).

Conflicts of interest

All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate

The study was conducted in strict accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of the Third Xiangya Hospital, Central South University, Changsha, China.

Consent for publication

Clinical data and peripheral blood sample were acquired from the patient after obtaining a written informed consent.


© The Author(s) 2023.


1. Bloem BR, Okun MS, Klein C. Parkinson’s disease. Lancet 2021;397:2284-303.

2. Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson’s disease. Lancet Neurol 2021;20:385-97.

3. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 2015;30:1591-601.

4. Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers 2017;3:17013.

5. Wang Q, Song S, Jiang L, Hon J. Interplay among norepinephrine, NOX2, and neuroinflammation: key players in Parkinson’s disease and prime targets for therapies. Ageing Neurodegener Dis 2021; 1:6.

6. Jankovic J, Tan EK. Parkinson’s disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry 2020;91:795-808.

7. Karabiyik C, Frake RA, Park SJ, Pavel M, Rubinsztein DC. Autophagy in ageing and ageing-related neurodegenerative diseases. Ageing Neurodegener Dis 2021;1:2.

8. Corti O, Lesage S, Brice A. What genetics tells us about the causes and mechanisms of Parkinson’s disease. Physiol Rev 2011;91:1161-218.

9. Deng H, Wang P, Jankovic J. The genetics of Parkinson disease. Ageing Res Rev 2018;42:72-85.

10. Blauwendraat C, Nalls MA, Singleton AB. The genetic architecture of Parkinson’s disease. Lancet Neurol 2020;19:170-8.

11. Jia F, Fellner A, Kumar KR. Monogenic Parkinson’s disease: genotype, phenotype, pathophysiology, and genetic testing. Genes (Basel) 2022;13:471.

12. Paisan-Ruiz C, Bhatia KP, Li A, et al. Characterization of PLA2G6 as a locus for dystonia-parkinsonism. Ann Neurol 2009;65:19-23.

13. Magrinelli F, Mehta S, Di Lazzaro G, et al. Dissecting the phenotype and genotype of PLA2G6-related parkinsonism. Mov Disord 2022;37:148-61.

14. Guo Y, Sun Y, Song Z, et al. Genetic analysis and literature review of SNCA variants in Parkinson’s disease. Front Aging Neurosci 2021;13:648151.

15. Yang J, Roy A, Zhang Y. Protein-ligand binding site recognition using complementary binding-specific substructure comparison and sequence profile alignment. Bioinformatics 2013;29:2588-95.

16. Yang J, Roy A, Zhang Y. BioLiP: a semi-manually curated database for biologically relevant ligand-protein interactions. Nucleic Acids Res 2013;41:D1096-103.

17. Forsell PK, Kennedy BP, Claesson HE. The human calcium-independent phospholipase A2 gene: multiple enzymes with distinct properties from a single gene. Eur J Biochem 1999;262:575-85.

18. Elsayed LEO, Eltazi IZ, Ahmed AE, Stevanin G. Insights into clinical, genetic, and pathological aspects of hereditary spastic paraplegias: a comprehensive overview. Front Mol Biosci 2021;8:690899.

19. Chu YT, Lin HY, Chen PL, Lin CH. Genotype-phenotype correlations of adult-onset PLA2G6-associated neurodegeneration: case series and literature review. BMC Neurol 2020;20:101.

20. Deng X, Yuan L, Jankovic J, Deng H. The role of the PLA2G6 gene in neurodegenerative diseases. Ageing Res Rev 2023;89:101957.

21. Cheng HL, Chen YJ, Xue YY, Wu ZY, Li HF, Wang N. Clinical characterization and founder effect analysis in Chinese patients with phospholipase A2-associated neurodegeneration. Brain Sci 2022;12:517.

22. Zou Y, Luo H, Yuan H, et al. Identification of a novel nonsense mutation in PLA2G6 and prenatal diagnosis in a Chinese family with infantile neuroaxonal dystrophy. Front Neurol 2022;13:904027.

23. Malley KR, Koroleva O, Miller I, et al. The structure of iPLA2β reveals dimeric active sites and suggests mechanisms of regulation and localization. Nat Commun 2018;9:765.

24. Ramanadham S, Ali T, Ashley JW, Bone RN, Hancock WD, Lei X. Calcium-independent phospholipases A2 and their roles in biological processes and diseases. J Lipid Res 2015;56:1643-68.

25. Larsson PK, Claesson HE, Kennedy BP. Multiple splice variants of the human calcium-independent phospholipase A2 and their effect on enzyme activity. J Biol Chem 1998;273:207-14.

26. Zhou Q, Yen A, Rymarczyk G, et al. Impairment of PARK14-dependent Ca2+ signalling is a novel determinant of Parkinson’s disease. Nat Commun 2016;7:10332.

27. Sánchez E, Azcona LJ, Paisán-Ruiz C. Pla2g6 deficiency in zebrafish leads to dopaminergic cell death, axonal degeneration, increased β-synuclein expression, and defects in brain functions and pathways. Mol Neurobiol 2018;55:6734-54.

28. Kinghorn KJ, Castillo-Quan JI, Bartolome F, et al. Loss of PLA2G6 leads to elevated mitochondrial lipid peroxidation and mitochondrial dysfunction. Brain 2015;138:1801-16.

29. Daida K, Nishioka K, Li Y, et al. PLA2G6 variants associated with the number of affected alleles in Parkinson’s disease in Japan. Neurobiol Aging 2021;97:147.e1-9.

30. Chen YJ, Chen YC, Dong HL, et al. Novel PLA2G6 mutations and clinical heterogeneity in Chinese cases with phospholipase A2-associated neurodegeneration. Parkinsonism Relat Disord 2018;49:88-94.

31. Chiu CC, Yeh TH, Lu CS, et al. PARK14 PLA2G6 mutants are defective in preventing rotenone-induced mitochondrial dysfunction, ROS generation and activation of mitochondrial apoptotic pathway. Oncotarget 2017;8:79046-60.

32. Gui YX, Xu ZP, Lv W, Liu HM, Zhao JJ, Hu XY. Four novel rare mutations of PLA2G6 in Chinese population with Parkinson’s disease. Parkinsonism Relat Disord 2013;19:21-6.

33. Engel LA, Jing Z, O'Brien DE, Sun M, Kotzbauer PT. Catalytic function of PLA2G6 is impaired by mutations associated with infantile neuroaxonal dystrophy but not dystonia-parkinsonism. PLoS One 2010;5:e12897.

34. Bohlega SA, Al-Mubarak BR, Alyemni EA, et al. Clinical heterogeneity of PLA2G6-related Parkinsonism: analysis of two Saudi families. BMC Res Notes 2016;9:295.

35. Lu CS, Lai SC, Wu RM, et al. PLA2G6 mutations in PARK14-linked young-onset parkinsonism and sporadic Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet 2012;159B:183-91.

Cite This Article

Export citation file: BibTeX | EndNote | RIS

OAE Style

Deng X, Zheng W, Yang Y, Yang Z, Li H, Song Z, Wang J, Deng H, Yuan L. Identification of PLA2G6 variants in a Chinese patient with Parkinson's disease. Ageing Neur Dis 2023;3:9.

AMA Style

Deng X, Zheng W, Yang Y, Yang Z, Li H, Song Z, Wang J, Deng H, Yuan L. Identification of PLA2G6 variants in a Chinese patient with Parkinson's disease. Ageing and Neurodegenerative Diseases. 2023; 3(2): 9.

Chicago/Turabian Style

Xinyue Deng, Wen Zheng, Yan Yang, Zhijian Yang, Huan Li, Zhi Song, Jiangang Wang, Hao Deng, Lamei Yuan. 2023. "Identification of PLA2G6 variants in a Chinese patient with Parkinson's disease" Ageing and Neurodegenerative Diseases. 3, no.2: 9.

ACS Style

Deng, X.; Zheng W.; Yang Y.; Yang Z.; Li H.; Song Z.; Wang J.; Deng H.; Yuan L. Identification of PLA2G6 variants in a Chinese patient with Parkinson's disease. Ageing. Neur. Dis. 2023, 3, 9.

About This Article

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (, which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Data & Comments




Comments must be written in English. Spam, offensive content, impersonation, and private information will not be permitted. If any comment is reported and identified as inappropriate content by OAE staff, the comment will be removed without notice. If you have any queries or need any help, please contact us at

Download PDF
Share This Article
Scan the QR code for reading!
See Updates
Ageing and Neurodegenerative Diseases
ISSN 2769-5301 (Online)


All published articles will be preserved here permanently:


All published articles will be preserved here permanently: