A new PLA2G6 mutation in a family with infantile neuroaxonal dystrophy

Abstract

Phospholipase A2-associated neurodegeneration (PLAN), a syndrome of Neurodegeneration with Brain Iron Accumulation (NBIA), is an autosomal recessive disorder caused by mutations in PLA2G6 gene. This gene encodes a calcium-independent group VI phospholipase A2 (iPLA-VI) critical in cell membrane homeostasis. PLAN syndrome encompasses a group of phenotypes with a different age of onset: classic infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy of childhood-onset (atypical NAD) and adult-onset PLA2G6-related dystonia-parkinsonism (PARK14). INAD is a severe progressive psychomotor disorder characterized by the presence of axonal spheroids throughout the central and peripheral nervous system. Here we report clinical, genetic and histopathological findings of an INAD consanguineous-family from Senegal. Sanger sequencing analysis revealed a new homozygous PLA2G6-mutation in the proband (c.1483C>T) and the co-segregation of the mutation in this family. Electron microscopy on skin biopsy showed degenerated axons confirming the phenotype. This study contributes to enrich the landscape of PLA2G6-associated INAD mutations and enforce the genotype-phenotype correlation.

Keywords: Axonal degeneration; Infantile neuroaxonal dystrophy; PLA2G6; mRNA nonsense-mediated decay.