%0 Journal Article
%T Novel deep intronic mutation in PLA2G6 causing early-onset Parkinson's disease with brain iron accumulation through pseudo-exon activation.
%A Cavestro C
%A Panteghini C
%A Reale C
%A Nasca A
%A Fenu S
%A Salsano E
%A Chiapparini L
%A Garavaglia B
%A Pareyson D
%A Di Meo I
%A Tiranti V
%J Neurogenetics
%V 22
%N 4
%D 10 2021
%M 34387792
%F 3.017
%R 10.1007/s10048-021-00667-0
%X PLA2G6 is the causative gene for a group of autosomal recessive neurodegenerative disorders known as PLA2G6-associated neurodegeneration (PLAN). We present a case with early-onset parkinsonism, ataxia, cognitive decline, cerebellar atrophy, and brain iron accumulation. Sequencing of PLA2G6 coding regions identified only a heterozygous nonsense variant, but mRNA analysis revealed the presence of an aberrant transcript isoform due to a novel deep intronic variant (c.2035-274G > A) leading to activation of an intronic pseudo-exon. These results expand the genotypic spectrum of PLAN, showing the paramount importance of detecting possible pathogenic variants in deep intronic regions in undiagnosed patients.