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

Area of Science:

• Neurogenetics
• Neurodevelopmental Disorders
• Dementia Etiology

Background:

• Methyl-binding domain protein 5 (MBD5) gene haploinsufficiency is linked to MBD5-neurodevelopmental disorders (MAND), typically presenting with intellectual disability, behavioral issues, and seizures.
• While MAND usually has a static course, some cases show regression, hinting at broader phenotypic possibilities.

Observation:

• A female patient without intellectual disability, but with a history of epilepsy and personality disorder, developed early-onset dementia.
• Genetic analysis identified a de novo heterozygous nonsense pathogenic variant in the MBD5 gene.

Findings:

• The identified MBD5 gene variant in a patient with atypical dementia expands the known clinical spectrum associated with MBD5 haploinsufficiency.
• This case highlights the potential role of MBD5 gene mutations in non-intellectually disabled individuals presenting with early-onset dementia.

Implications:

• Suggests that the MBD5 gene should be considered in the etiological investigation of patients with atypical early-onset dementia, even in the absence of intellectual disability.
• Broadens the understanding of MBD5-related disorders and their potential neurological manifestations beyond typical developmental delays.