Homozygous MAPT R406W mutation causing FTDP phenotype: A unique instance of a unique mutation

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Frontotemporal dementia (FTD) is a group of neurodegenerative disorders.
• Autosomal-dominant frontotemporal dementia and parkinsonism linked to chromosome 17q21.2 (FTDP-17) is a known subtype.
• Mutations in the MAPT gene are a primary cause of FTDP-17.

Observation:

• The R406W mutation in the MAPT gene has been previously associated with Alzheimer's-like phenotypes.
• This study reports the first homozygous R406W mutation in an Iranian family.
• The observed phenotype in this family presented with characteristics of FTD.

Findings:

• Homozygous R406W MAPT mutation can manifest as FTD.
• This finding expands the known clinical spectrum of MAPT mutations.
• Clinical heterogeneity among MAPT mutations, including R406W, is confirmed.

Implications:

• This case highlights the importance of genetic testing in diagnosing FTD.
• The study suggests a potential dosage effect of the R406W mutation contributing to phenotypic variability.
• Further research into MAPT mutation dosage effects is warranted for understanding FTD pathogenesis.