Whole-exome sequencing reveals PSEN1 and ATP7B combined variants as a possible cause of early-onset Lewy body dementia: a case study of genotype-phenotype correlation

Neurogenetics. 2022 Oct;23(4):279-283. doi: 10.1007/s10048-022-00699-0. Epub 2022 Sep 17.

Abstract

Dementia with Lewy bodies is a neurodegenerative disease, sharing features with Parkinson's and Alzheimer's diseases. We report a case of a patient dementia with Lewy bodies carrying combined PSEN1 and ATP7B mutations. A man developed dementia with Lewy bodies starting at the age of 60 years. CSF biomarkers were of Alzheimer's disease and DaTSCAN was abnormal. Whole-exome sequencing revealed a heterozygous p.Ile408Thr PSEN1 variant and a homozygous p.Arg616Trp ATP7B variant. This case reinstates the need of considering ATP7B mutations when evaluating a patient with parkinsonism and supports p.Ile408Thr as a pathogenic PSEN1 variant.

Keywords: Alzheimer; Copathology; Genetics; Lewy body dementia; Synuclein; Wilson’s disease.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / complications
  • Alzheimer Disease* / genetics
  • Exome Sequencing
  • Genetic Association Studies
  • Humans
  • Lewy Body Disease* / complications
  • Lewy Body Disease* / genetics
  • Neurodegenerative Diseases*
  • Presenilin-1 / genetics

Substances

  • PSEN1 protein, human
  • Presenilin-1