To describe the FTDP-17 family.

In 2006 a c.823-10G>T MAPT variant in intron 9 resulting in the inclusion of exon 10 in the MAPT transcript and overexpression of 4R tau was reported in a family with FTDP-17 (Malkani et al, 2006- single report to date).

The study submitted for AAN is the first study with autopsy results and the only other report of this variant to date.

Examination and MAPT Sanger: proband, two asymptomatic siblings.

MRI brain: proband.

Autopsy: proband, brother.

Clinical:

A 50-year-old man behaved inappropriately (diagnosed FTDP-17 at 61). He became wheelchair bound, anarthric and recently died (this allowed for the second autopsy analysis).

The proband’s brother became “odd” in his 40s, forgetful (diagnosed FTD, died at 59).

Brother: dementia in his 40s, “odd”, died at 53.

The proband’s sister and maternal aunt: forgetful,  vulgar.

The pro band’s mother: dementia in late 70s, father at 43 was forgetful, had sweet tooth and died at 53.

Radiological:

Proband MRI brain: very severe temporal and frontal lobes atrophy.

Neuropathological:

Proband: severe atrophy of the frontal and temporal lobes. Frequent tau pathology.  

Brother: Tau antibody staining- 4R tauopathy.

Western blot:

Brother: blots of the sarkosyl-insoluble tau extracted from three brain regions showed that the insoluble pathological tau was exclusively 4R-tau.

Sanger:

Proband: heterozygote for the splicing mutation c.823-10G>T at the intron 9/ exon 10 boundary of the tau (MAPT) gene. Not detected in two asymptomatic siblings.