A study of mostly Turkish families. One patient in a screen of 98 families carried this variant; this patient had been diagnosed with Alzheimers Disease, age at onset 77 years. Overall, 56 families were diagnosed with AD, 31 with mild cognitive impairment, and the remainder with frontotemporal dementia (8), Lewy body disease (4), Parkinson disease with dementia (3), or atypical or mixed types of dementia (4). The study examined APP (exons 16 and 17), PSEN1 (exons 3–12), and PSEN2 (exons 3–12), as well as the flanking intronic sequences.
The authors note that segregation with the disease in this family could not be established. They note that all variant carriers reported to date had late onset AD (72-81 years) and slow progressing cognitive impairment. They classify the variant as “probably pathogenic”.
EVS data describes 9 out of 5370 samples as carrying this variant heterozygously (0.2% of individuals). We don’t know the phenotypes of these individuals, but Lohmann et al’s observation has no statistically significant enrichment compared to this population.