Overview

Pathogenicity: Other Tauopathy : Pathogenic
Clinical Phenotype: Tauopathy with Parkinsonism and Motor Neuron Disease
Reference Assembly: GRCh37 (105)
Position: Chr17:44091643 A>T
dbSNP ID: rs63750092
Coding/Non-Coding: Coding
Genomic Region: Exon 11
Mutation Type: Point, Missense
Codon Change: AAG to ATG

Findings

The K317M mutation was identified in two genetically related families from Basque, Spain. The 13 affected individuals in these families presented with symptoms such as dysarthria (difficulty speaking), tremor, and other motor features such as parkinsonism, pyramidalism, and amyotrophy (progressive, painful muscle wasting). The mean age at onset was 48 years and the mean disease duration was six years. In these families the mutation is associated with FTDP-17 and causes a tauopathy with parkinsonism, motor neuron disease, and frontotemporal degeneration (Zarranz et al., 2005).

Neuropathology

Autopsy showed severe degeneration of the substantia nigra with extensive neuronal loss and gliosis. No Lewy bodies or Pick’s bodies were observed. Particularly severe neuron loss was noted in the motor bulbar nuclei and in the anterior horn of the spinal cord. Frequent, diverse inclusions were present in oligodendrocytes and astrocytes, and neurons contained phospho-tau-positive pre-tangles and tangles (Zarranz et al., 2005).

Biological Effect

Unknown.

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References

Paper Citations

1. Zarranz JJ, Ferrer I, Lezcano E, Forcadas MI, Eizaguirre B, Atarés B, Puig B, Gómez-Esteban JC, Fernández-Maiztegui C, Rouco I, Pérez-Concha T, Fernández M, Rodríguez O, Rodríguez-Martínez AB, de Pancorbo MM, Pastor P, Pérez-Tur J. A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease. Neurology. 2005 May 10;64(9):1578-85. PubMed.

Further Reading

Learn More

1. Alzheimer Disease & Frontotemporal Dementia Mutation Database