<i>PLA2G6</i> Mutations Related to Distinct Phenotypes: A New Case with Early-onset Parkinsonism

  • Anamika Giri
  • Gamze Guven
  • Hasmet Hanagasi
  • Ann-Kathrin Hauser
  • Nihan Erginul-Unaltuna
  • Basar Bilgic
  • Hakan Gurvit
  • Peter Heutink
  • Thomas Gasser
  • Ebba Lohmann
  • Javier Simón-Sánchez

Abstract

Background: PLA2G6-associated neurodegeneration (PLAN) is a recessive neurodegenerative disorder characterized by three distinct phenotypes: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (atypical NAD), and PLA2G6-related dystonia–parkinsonism.

Methods: A consanguineous index case from Turkey was diagnosed with early-onset Parkinsonism at the Istanbul Faculty of Medicine. She and her unaffected brother were subjected to whole-genome sequencing.

Results: In this report, we describe a 33-year-old index case with parental consanguinity and early-onset Parkinsonism. Whole-genome sequencing of this individual revealed that a homozygous p.R747W mutation in PLA2G6 segregates with the disease in this family

Discussion: This result supports the importance of prioritizing this gene in mutational analysis of autosomal recessive Parkinsonism, and confirms the clinical heterogeneity of PLAN.