Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Reference Assembly: GRCh37 (105)
Position: Chr17:44096052 T>A
dbSNP ID: NA
Coding/Non-Coding: Coding
Genomic Region: Exon 12
Mutation Type: Point, Missense
Codon Change: TCC to ACC

Findings

This mutation has been reported in two family members affected by the behavioral variant of frontotemporal dementia (bvFTD) (Momeni et al., 2010). The proband developed behavioral symptoms at age 29, including disinhibition, theft, and stereotyped behavior. She was initially diagnosed with schizophrenia, but her diagnosis was later corrected to bvFTD. The proband’s father was also a mutation carrier. He was diagnosed with schizophrenia at the age of 27 following changes in personality and behavior including aggression and apathy. He died at age 42; postmortem examination revealed neuropathology consistent with bvFTD (see below). The mutation was absent in three unaffected family members (the proband’s mother and two paternal siblings), suggesting segregation with disease.

Neuropathology

Autopsy revealed frontotemporal lobar degeneration and hippocampal atrophy. Some spongiosis was noted in the cortex. Abundant tau pathology, including mature neurofibrillary tangles was observed, especially in the cortex, hippocampus, and substantia nigra. Pretangles were more widespread. Tau-positive threads and grains were also noted. Beta-amyloid pathology was largely absent.

Biological Effect

Unknown.

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References

Paper Citations

1. Momeni P, Wickremaratchi MM, Bell J, Arnold R, Beer R, Hardy J, Revesz T, Neal JW, Morris HR. Familial early onset frontotemporal dementia caused by a novel S356T MAPT mutation, initially diagnosed as schizophrenia. Clin Neurol Neurosurg. 2010 Dec;112(10):917-20. PubMed.

Further Reading