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Identification Of The Ps1 Thr147ile Variant In A Family With Very Early Onset Dementia And Expressive Aphasia, James Denvir, Shirley Neitch, Jun Fan, Richard M. Niles, Goran Boskovic, Bernard G. Schreurs, Donald A. Primerano, Daniel L. Alkon

Biochemistry and Microbiology

Background: Early onset dementias have variable clinical presentations and are often difficult to diagnose. We established a family pedigree that demonstrated consistent recurrence of very early onset dementia in successive generations.

Objective and Method: In order to refine the diagnosis in this family, we sequenced the exomes of two affected family members and relied on discrete filtering to identify disease genes and the corresponding causal variants.

Results: Among the 720 nonsynonymous single nucleotide polymorphisms (SNPs) shared by two affected members, we found a C to T transition that gives rise to a Thr147Ile missense substitution in the presenilin 1 (PS1) …