A novel combined heterozygous mutation in the PLA2G6 gene associated with early-onset Parkinson’s disease

Objectives PLA2G6-associated neurodegeneration(PLAN) is a rare,heterogeneous group of neurodegenerative disorders caused by homozygous mutations in the PLA2G6 gene.Infantile neuroaxonal dystrophy(INAD),atypical neuroaxonal dystrophy(ANAD) and autosomal recessive early-onset Parkinson's disease(EOPD) are the subtypes of PLAN according to age of onset and clinical features. Methods A 7-year-old female patient presented with hand tremor,gait abnormality,posture balance disturbance and scanned speech which had been noticed for nearly 3 months.Pregnancy and delivery were unremarkable and family history was noncontributory.Her neurological examination revealed postural tremor, dystonia and gait ataxia.Laboratory analyses revealed no abnormalities in blood chemistry and metabolic screening.Cranial magnetic resonance imaging (MRI)revealed iron accumulation in the mesencephalon and globus pallidus.She was put on levodopa treatment and SLC2A,PANK2 gene analysis were examined respectively.Whole Exome Sequencing revealed two new,previously unidentified,c.1630A>G p.M544V and c.1748T>C p.M583T heterozygous mutations in the PLA2G6 gene.Insilico analyzes shows that mutations are pathogenic and the mother was heterozygous for c.1630A>G p.M544V and the father was heterozygous for c.1748T>C p.M583T. Discussion INAD and ANAD are seen in childhood with cerebellar cortical atrophy and iron deposition that are called neurodegeneration with brain accumulation type II(NIBA).EOPD is an early adult onset disease and typically characterized wtih dystonia,rapid cognitive decline,psychosis,dysarthria and pyramidal symptoms.Besides this,it has been reported that PLAN can be occur with some intermediate phenotypes other than the classical disease pattern,genotype-phenotype association can not be made clearly. Conclusion It is aimed to draw attention to the fact that the spectrum of PLA2G6-related disease that starts in young adulthood can be variable and can be seen at early ages.
Keywords: PLA2G6, early-onset Parkinson, dystonia, childhood