Precis Future Med.  2019 Sep;3(3):135-138. 10.23838/pfm.2019.00086.

Intrafamilial variability and clinical heterogeneity in a family with PLA2G6-associated neurodegeneration

• Park JK
• Youn J
• Cho JW

• KMID: 2465835
• DOI: http://doi.org/10.23838/pfm.2019.00086

Abstract

Phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN) is an autosomal recessive neurodegenerative disease with a wide clinical spectrum; however, the genotype-phenotype correlation is unknown. Here, we report different phenotypes in one family with the same genotype. A 28-year-old male presented with slowly progressive gait disturbance with spasticity. Onset occurred at 11 years. Interestingly, his younger brother, a 24-year-old male, presented with progressive Parkinsonism, which began at 22 years. He showed excellent response to levodopa but developed a fluctuating medication response and levodopa-induced dyskinesia 1 year after starting levodopa medication. He also demonstrated hyperreflexia, but no spasticity. Dopamine transporter imaging showed reduced uptake in the bilateral putamen. In whole-exome sequencing and Sanger sequencing, a homozygous pathogenic variant (p. R747W) in the PLA2G6 gene was detected in both cases. Despite different clinical features, both subjects had hyperreflexia during the examination and claval hypertrophy was shown on the brain magnetic resonance imaging.

Keyword

PLA2G6; Parkinson disease; Genetic analysis

MeSH Terms

Adult
Brain
Dopamine Plasma Membrane Transport Proteins
Dyskinesias
Gait
Genetic Association Studies
Genotype
Humans
Hypertrophy
Levodopa
Magnetic Resonance Imaging
Male
Muscle Spasticity
Neuroaxonal Dystrophies*
Neurodegenerative Diseases
Parkinson Disease
Parkinsonian Disorders
Phenotype
Phospholipases A2
Population Characteristics*
Putamen
Reflex, Abnormal
Siblings
Young Adult
Dopamine Plasma Membrane Transport Proteins
Levodopa
Phospholipases A2