A de novo, mosaic and complex chromosome 21 rearrangement causes APP triplication and familial autosomal dominant early onset Alzheimer disease.

ABSTRACT: Copy number variation (CNV) of the amyloid-β precursor protein gene (APP) is a known cause of autosomal dominant Alzheimer disease (ADAD), but de novo genetic variants causing ADAD are rare. We report a mother and daughter with neuropathologically confirmed definite Alzheimer disease (AD) and extensive cerebral amyloid angiopathy (CAA). Copy number analysis identified an increased number of APP copies and genome sequencing (GS) revealed the underlying complex genomic rearrangement (CGR) including a triplication of APP with two unique breakpoint junctions (BPJs). The mosaic state in the mother had likely occurred de novo. Digital droplet PCR (ddPCR) on 42 different tissues, including 17 different brain regions, showed the derivative chromosome at varying mosaic levels (20-96%) in the mother

SUBMITTER: Ehn E 

PROVIDER: S-EPMC11759332 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature