Mutations

MAPT L266V

Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Genomic Mutation Name (MET1): g.110044C>G
Genomic Mutation Name (NT1): g.107218C>G
dbSNP ID: rs63750349
Coding/Non-Coding: Coding
Genomic Region: Exon 9
Mutation Type: Point, Missense
Codon Change: CTG to GTG

Findings

This mutation was originally identified in a Japanese man who developed difficulties speaking and reading at age 34. He developed a rapidly progressive frontotemporal dementia with personality changes, disorientation, and semantic dementia. He died at age 40. The proband's mother developed personality changes at age 31 and died at age 36. The proband's brother developed personality changes and apathy at age 38. Both affected siblings carried the mutation. DNA from the mother was unavailable, but it is thought that this mutation causes an aggressive familial form of frontotemporal dementia (Kobayashi et al., 2002).

Neuropathology

Severe atrophy of the frontal and temporal lobes. Many tau-positive inclusions, including Pick bodies. Tau-positive, argyrophilic astrocytes with stout filaments and round or irregular argyrophilic inclusions. Severe neuronal loss and gliosis (Kobayashi et al., 2002; Hogg et al., 2003).

Biological Effect

Elevated levels of exon 10+ tau mRNA and soluble 4-repeat (4R) tau. Decreased rate and extent of tau-induced microtubule assembly. A 3R isoform-specific increase in tau self-assembly (Kobayashi et al., 2002; Hogg et al., 2003).

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References

Paper Citations

  1. . A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau pathology. Ann Neurol. 2003 Jan;53(1):133-7. PubMed.
  2. . The L266V tau mutation is associated with frontotemporal dementia and Pick-like 3R and 4R tauopathy. Acta Neuropathol. 2003 Oct;106(4):323-36. Epub 2003 Jul 19 PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau pathology. Ann Neurol. 2003 Jan;53(1):133-7. PubMed.
  2. . The L266V tau mutation is associated with frontotemporal dementia and Pick-like 3R and 4R tauopathy. Acta Neuropathol. 2003 Oct;106(4):323-36. Epub 2003 Jul 19 PubMed.

Other mutations at this position

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