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

Abstract

Phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN) includes a series of neurodegenerative diseases that result from the mutations in PLA2G6. PLAN has genetic and clinical heterogeneity, with different mutation sites, mutation types and ethnicities and its clinical phenotype is different. The clinical phenotypes and genotypes of PLAN are closely intertwined and vary widely. PLA2G6 encodes a group of VIA calcium-independent phospholipase A2 proteins (iPLA₂β), an enzyme involved in lipid metabolism. According to the age of onset and progressive clinical features, PLAN can be classified into the following subtypes: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD) and parkinsonian syndrome which contains adult onset dystonia parkinsonism (DP) and autosomal recessive early-onset parkinsonism (AREP). In this review, we present an overview of PLA2G6-associated neurodegeneration in the context of current research.

Keywords: ANAD; AREP; DP; INAD; PLA2G6; PLAN; iPLA2β.

Figure 1

Identified mutation sites of PLA2G6 gene. (A) There are 17 exons of the PLA2G6 gene, and mutation sites were distributed on the exons. (B) Schematic representation in scale of the full-length iPLA2β protein with functional regions and position of the variant protein. The mutations which cause dystonia-parkinsonism, previously identified by others, are shown above. 1–7 = ankyrin repeat region. The position of calmodulin domains and motifs was provided by https://www.uniprot.org/uniprot/O60733. Red, INAD; Blue, ANAD; Green, DP; Yellow, NBIA; Purple, parkinsonian syndrome.