Open AccessWASHC5 mutation extends the genotypic heterogeneity in early-onset Parkinson’s disease
Author(s) -
Cyprian Popescu
Publication year - 2022
Publication title -
future neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 32
eISSN - 1748-6971
pISSN - 1479-6708
DOI - 10.2217/fnl-2021-0009
Subject(s) - hereditary spastic paraplegia , genetics , mutation , parkinson's disease , disease , genotype , genetic heterogeneity , exome sequencing , neurogenetics , exome , allele , biology , medicine , gene , phenotype
Materials & methods: Herein, we are reporting a 31-year-old man diagnosed with Parkinson’s disease (PD) without evidence of family co-segregation. Analysis across the PD loci was carried out followed by whole-exome sequencing. Results: We identified a novel heterozygous WASHC5 variant, c.775T >C p. (Tyr259His) segregating with PD. WASHC5 or strumpellin has previously been identified in autosomal dominant disorder hereditary spastic paraplegia type 8 (HSP8). Conclusion: We present clinical, genetic and physiopathological data supporting a relevant role of c.775T >C p. (Tyr259His) variant in early-onset PD. One can hypothesizes a model wherein the clinical continuum of strumpellin-associated neurological syndromes share common pathways based on endo-lysosomal trafficking dysfunction. This novel mutation extends the spectrum of WASHC5 gene mutations and supports the allelic heterogeneity of PD.