Mutations

MAPT N296del (ΔN296)

Overview

Pathogenicity: Other Tauopathy : Pathogenic, Frontotemporal Dementia : Not Pathogenic
Clinical Phenotype: Progressive Supranuclear Palsy
Genomic Mutation Name (MET1): g.123775_123777delATA
Genomic Mutation Name (NT1): g.120954_120956delATA
dbSNP ID: rs63751392
Coding/Non-Coding: Coding
Genomic Region: Exon 10
Mutation Type: Deletion
Codon Change: ATA to -

Findings

This mutation was originally identified in a Spanish kindred in which two brothers were affected with atypical progressive supranuclear palsy. A homozygous deletion at codon 296 (N296del) was identified in one of the brothers. In heterozygous individuals, this mutation is incompletely penetrant and associated with a phenotype similar to idiopathic Parkinson's disease (Pastor et al., 2001).

Neuropathology

Atrophy of the right precentral gyrus and the brainstem were observed, as well as neuron loss and gliosis in the substantia nigra, several nuclei of the brainstem, and diencephalon. Hyperphosphorylated tau and neurofibrillary tangles accumulate in neurons in many brain regions. Tau also accumulates in astrocytes and oligodendrocytes (Ferrer et al., 2003).

Biological Effect

The N296del mutation has little or no effect on exon 10 splicing, but substantially reduces the ability of tau to promote microtubule assembly and increases aggregation of tau into filaments (Grover et al., 2002).

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References

Paper Citations

  1. . Familial atypical progressive supranuclear palsy associated with homozigosity for the delN296 mutation in the tau gene. Ann Neurol. 2001 Feb;49(2):263-7. PubMed.
  2. . Tau phosphorylation and kinase activation in familial tauopathy linked to deln296 mutation. Neuropathol Appl Neurobiol. 2003 Feb;29(1):23-34. PubMed.
  3. . Effects on splicing and protein function of three mutations in codon N296 of tau in vitro. Neurosci Lett. 2002 Apr 19;323(1):33-6. PubMed.

Further Reading

Papers

  1. . Functional effects of tau gene mutations deltaN296 and N296H. J Neurochem. 2002 Feb;80(3):548-51. PubMed.

Learn More

Primary Papers

  1. . Familial atypical progressive supranuclear palsy associated with homozigosity for the delN296 mutation in the tau gene. Ann Neurol. 2001 Feb;49(2):263-7. PubMed.

Other mutations at this position

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