Early-Onset Dementia Associated with a Heterozygous, Nonsense, and de novo Variant in the MBD5 Gene

J Alzheimers Dis. 2021;84(1):73-78. doi: 10.3233/JAD-210648.

Abstract

The haploinsufficiency of the methyl-binding domain protein 5 (MBD5) gene has been identified as the determinant cause of the neuropsychiatric disorders grouped under the name MBD5-neurodevelopment disorders (MAND). MAND includes patients with intellectual disability, behavioral problems, and seizures with a static clinical course. However, a few reports have suggested regression. We describe a non-intellectually disabled female, with previous epilepsy and personality disorder, who developed early-onset dementia. The extensive etiologic study revealed a heterozygous nonsense de novo pathogenic variant in the MBD5 gene. This finding could support including the MBD5 gene in the study of patients with atypical early-onset dementia.

Keywords: Early-onset dementia; MBD5-neurodevelopment disorders; gene; human phenotype ontology; methyl-binding domain protein 5 (MBD5); personality disorder; seizures.

Publication types

  • Case Reports
  • Letter

MeSH terms

  • Codon, Nonsense*
  • DNA-Binding Proteins / genetics*
  • Dementia* / etiology
  • Dementia* / genetics
  • Epilepsy / complications
  • Female
  • Heterozygote
  • Humans
  • Middle Aged
  • Mutation / genetics*
  • Neuropsychological Tests / statistics & numerical data
  • Personality Disorders / complications
  • Phenotype
  • Positron Emission Tomography Computed Tomography
  • Problem Behavior / psychology

Substances

  • Codon, Nonsense
  • DNA-Binding Proteins
  • MBD5 protein, human