Early-Onset Parkinson's Disease Caused by PLA2G6 Compound Heterozygous Mutation, a Case Report and Literature Review

Abstract

PLA2G6 has been certified as a causative gene in patients with autosomal recessive early-onset Parkinson's disease (EOPD). We reported an EOPD case caused by PLA2G6 gene mutation, and performed neurological examination, genetic analysis, and multimodal neuroimaging to describe this phenotype. A compound heterozygous mutation c.991G>T/c.1472+1G>A was detected in this patient. Heterozygous for the c.991G>T and c.1472+1G>A were separately detected in his parents. Pathogenicity of these two mutations were predicted according to the American college of medical genetics and genomics (ACMG) guideline. MRI assessment showed absence of bilateral “swallow tail sign” and cerebellar atrophy in this patient, while no obvious difference in brain iron accumulation between PLA2G6 mutant PD patient and healthy controls. Cerebellar abnormalities may be a marker for diagnosis and evaluation of PLA2G6 mutation Parkinsonism. However, the iron accumulation in PD may not be the result of PLA2G6 mutation.

Severe Early‐Onset Parkinsonian Syndrome Caused by PLA2G6 Heterozygous Variants

“…Pathogenic PLA2G6 variants are among the causes of early‐onset parkinsonism 8 . They have been described in homozygosity or in compound heterozygosity 9,10 . NBIA/DYT/PARK‐ PLA2G6 is a rare autosomal recessive disease with a wide variety of clinical manifestations.…”

Primate differential redoxome (PDR) – A paradigm for understanding neurodegenerative diseases

“…PLA2G6 dysfunction causes PLA2G6-associated neurodegenerations (PLAN), including infantile neuroaxonal dystrophy (INAD), neurodegeneration with brain iron accumulation (NBIA), and PLA2G6-related autosomal recessive dystonia-parkinsonism. Mutations in PLA2G6 are also associated with atypical autosomal recessive parkinsonism, and sporadic early-onset PD [ 49 ].…”

Overdosing on iron: Elevated iron and degenerative brain disorders

“…In this context it is interesting that compound mutations in the PLA2G6 gene have been suggested to cause autosomal recessive earlyonset PD. 471,472 PLA2G6 knockout mice develop progressive motor impairment in their second year of life. [473][474][475][476] Like patients, these mice display neuropathological features including damaged mitochondria, axonal degeneration, cerebellar atrophy, accumulation of a-synuclein-containing and ubiquitin-positive spheroids in axons in nearly all brain regions.…”

“…In this context it is interesting that compound mutations in the PLA2G6 gene have been suggested to cause autosomal recessive early-onset PD. 471,472…”