Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Reference Assembly: GRCh37/hg19
Position: Chr17:44087783 A>C
Coding/Non-Coding: Non-Coding
DNA Change: Substitution
Expected RNA Consequence: Splicing Alteration
Expected Protein Consequence: Isoform Shift
Codon Change: A to C
Genomic Region: Intron 10


This intronic point mutation was identified in a large Irish family affected by frontotemporal dementia (McCarthy et al., 2015). The reported pedigree shows 21 affected individuals over four generations and a pattern of inheritance consistent with autosomal-dominant transmission. The mutation segregated with disease in this family. Among five siblings, it was detected in the three symptomatic siblings and absent in the two who were asymptomatic. In general, affected family members presented with a behavioral syndrome typical for the behavioral variant of FTD along with episodic memory loss. One sister presented first with parkinsonism and eyelid apraxia without cognitive or behavioral changes.


Unknown. FDG-PET imaging in the Irish proband showed bilateral anterior temporal lobe atrophy and hypometabolism (McCarthy et al., 2015).

Biological Effect

This mutation occurs within intron 10. It is located within the intronic sequence known to form the “stem” of the hairpin-loop structure at the boundary of intron 10 and exon 10. In vitro, the mutation causes a shift in tau splicing that favors the inclusion of exon 10 in transcripts. This is predicted to result in greater production of tau isoforms containing 4-microtubule binding repeat domains (4R tau) and fewer isoforms containing three-repeat domains (3R tau) (McCarthy et al., 2015).

Last Updated: 04 Sep 2015


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Paper Citations

  1. . Closing the tau loop: the missing tau mutation. Brain. 2015 Oct;138(Pt 10):3100-9. Epub 2015 Aug 21 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Closing the tau loop: the missing tau mutation. Brain. 2015 Oct;138(Pt 10):3100-9. Epub 2015 Aug 21 PubMed.


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