The role of the PLA2G6 gene in neurodegenerative diseases

Deng, Xinyue; Yuan, Lamei; Jankovic, Joseph; Deng, Hao

doi:10.1016/j.arr.2023.101957

Cited by 11 publications

(5 citation statements)

References 85 publications

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“…However, cerebellar atrophy and iron accumulation also can be found in several other diseases ( 6 ). Besides, iron accumulation appears only at the late stage of INAD ( 4 , 5 ). In the patient with PLA2G6 c.1778C>T/c.1974C>A compound heterozygous variants, brain iron accumulation was absent at age of 2 years ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…Our findings also indicated reduced creatinine levels and elevated ALP/CK-MB levels in the proband, indicating a widespread enzyme metabolism disorder and, possibly, kidney, heart, and multiple tissue damage. Furthermore, axon spheroids and vacuoles revealed by peripheral nerve biopsies have long been regarded as a gold standard for INAD diagnosis, with an estimated 87% of PLA2G6 mutation-positive INAD having axon spheroids ( 5 ). However, parents of INAD children have a less than enthusiastic response to cooperating with peripheral nerve biopsies, once they are informed of its invasive procedures, at least in our case.…”

Section: Discussionmentioning

confidence: 99%

“…Infants with typical INAD usually experience a short asymptomatic period after birth ( 4 ). Most of them, from the age of 6 months or even earlier, consistently develop multiple neuropathological symptoms, including but not limited to progressive psychomotor deterioration, mental retardation, axial hypotonia, cerebellar ataxia, hearing loss (HL), and optic nerve abnormalities, that jointly lead to a persistent vegetative state and premature death, generally early in the first decade of life ( 4 , 5 ). There is growing evidence that INAD is primarily caused by various loss-of-function variants in the phospholipase A2 group VI ( PLA2G6 ) gene on chromosome 22q, while genetic and phenotypic heterogeneity exists ( 6 - 10 ).…”

Section: Introductionmentioning

confidence: 99%

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A rare inherited homozygous missense variant in PLA2G6 influences susceptibility to infantile neuroaxonal dystrophy: a case report

Lyu,

Wang,

Lin

et al. 2024

Transl Pediatr

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Background Infantile neuroaxonal dystrophy (INAD) is an ultra-rare early-onset autosomal recessive neurodegenerative disorder due to PLA2G6 variants. The clinical symptoms of INAD patients display considerable diversity, and many PLA2G6 variants are still not thoroughly investigated in relation to their associated clinical presentations. Case Description A 16-month-old boy was admitted to our hospital due to regression of acquired motor and speech abilities that had persisted for 4 months. The patient was born to a healthy consanguineous couple after 41 weeks of pregnancy and natural delivery. Before 12 months old, he had normal motor development milestones. On admission, he also showed astasia-abasia, weakness of distal muscles, and diminished patellar tendon reflex. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy. Auditory brainstem response (ABR) indicated moderately severe hearing loss. With chromosome microarray analysis (CMA), we identified several copy number-neutral regions of runs of homozygosity (ROH) in the patient. Whole-exome sequencing (WES) further revealed that the patient harbored a homozygous missense variant NM_003560.2: c.1778C>T, p.Pro593Leu (rs1451486649) in the PLA2G6 gene. In the patient’s asymptomatic parents and brother, the PLA2G6 c.1778C>T variant stayed in heterozygous status as confirmed by Sanger sequencing. The patient was finally diagnosed with INAD. Conclusions We report an INAD child with a rare PLA2G6 c.1778C>T homozygous missense variant and associated clinical symptoms. The family-based cosegregation analysis reveals that the PLA2G6 c.1778C>T homozygous variant contributes to the pathogenesis of INAD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A rare inherited homozygous missense variant in PLA2G6 influences susceptibility to infantile neuroaxonal dystrophy: a case report

Lyu,

Wang,

Lin

et al. 2024

Transl Pediatr

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“…circABCC4 promotes BPD progression by facilitating PLA2G6 expression by sequestering miR-663a ( Chen et al, 2020 ). PLA2G6, which belongs to the phospholipase A2 family that is involved in signal transduction and phospholipid homeostasis ( Deng et al, 2023 ), further aggravates lung inflammation by promoting the production of arachidonic acid metabolites ( Bellido-Reyes et al, 2006 ). circABPD1 was also found highly expressed in preterm colostrum milk exosomes, it can alleviate lung injury by targeting the miR-330–3p/HIF1α axis ( Li et al, 2023 ).…”

Section: Circrnas In Lung Developmentmentioning

confidence: 99%

Functional roles of circular RNAs in lung injury

Gao,

Chen,

Jiang

et al. 2024

Front. Pharmacol.

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Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

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“…Autosomal recessive EOP caused by mutations in the PLA2G6 gene is called PLA2G6-associated Neurodegeneration (PLAN) ( 2 , 3 ). These include Infantile neuroaxonal dystrophy (INAD), Atypical neuroaxonal dystrophy (ANAD), and EOP ( 4 ). In this study, a case of EOP caused by a novel PLA2G6 gene mutation was reported, and previous reports of EOP related to this gene were reviewed.…”

Section: Introductionmentioning

confidence: 99%

A novel variant of PLA2G6 gene related early-onset parkinsonism: a case report and literature review

Cai,

Wu,

Huang

et al. 2024

Front. Neurol.

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This study reported a case of early-onset parkinsonism associated with a novel variant of the PLA2G6 gene. The boy first started showing symptoms at the age of 11, with gait instability and frequent falls. As the disease progressed, his gait instability worsened, and he developed difficulties with swallowing and speaking, although there was no apparent decline in cognitive function. An MRI of the head revealed significant atrophy of the cerebellum. The initial diagnosis for the boy was early-onset parkinsonism, classified as Hoehn-Yahr grade 5.Genomic sequencing of the patient indicated that he had compound heterozygous variations in the PLA2G6 gene: c.1454G>A (p.Gly485Glu) and c.991G>T (p.Asp331Tyr). Pedigree analysis revealed that his younger brother also carried the same variant, albeit with milder symptoms. The patient's unaffected mother was found to be a carrier of the c.991G>T variant. Additionally, this study reviewed 62 unrelated families with PLA2G6 gene-related early-onset parkinsonism. The analysis showed a higher proportion of female probands, with a mean age of onset of ~23.0 years. Primary symptoms were predominantly bradykinesia and psychosis, with tremors being relatively rare. Cerebellar atrophy was observed in 41 patients (66.1%). Among the reported mutations, the most common mutation was c.991G>T, presenting in 21 families (33.9%), followed by c.2222G>A in eight families (12.9%). Other mutations were less common. Notably, the c.991G>T mutation was exclusive to Chinese families and was a prevalent mutation among this population. The initial symptoms varied significantly among patients with different mutations.

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The role of the PLA2G6 gene in neurodegenerative diseases

Cited by 11 publications

References 85 publications

A rare inherited homozygous missense variant in PLA2G6 influences susceptibility to infantile neuroaxonal dystrophy: a case report

A rare inherited homozygous missense variant in PLA2G6 influences susceptibility to infantile neuroaxonal dystrophy: a case report

Functional roles of circular RNAs in lung injury

A novel variant of PLA2G6 gene related early-onset parkinsonism: a case report and literature review

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