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[P2–114]: PATIENT‐DERIVED IPSC MODEL OF AN ABCA7 FRAMESHIFT DELETION ASSOCIATED WITH ALZHEIMER's DISEASE IN AFRICAN AMERICANS
Author(s) -
Cukier Holly N.,
Mehta Neil,
Ramirez Juliana,
Rolati Sophie,
Whitehead Patrice L.,
Deon Adams Larry,
Celis Katrina,
Carney Regina,
Vance Jeffery M.,
Cuccaro Michael L.,
Byrd Goldie S.,
PericakVance Margaret A.,
Dykxhoorn Derek M.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.764
Subject(s) - frameshift mutation , biology , induced pluripotent stem cell , allele , genetics , mutation , gene , embryonic stem cell
Background:Patients with early-onset Alzheimer’s disease (EOAD) are relatively rare. APP, PSEN1 and PSEN2, are major causative factors for the disease progression. Patient was a 37 years old male, who was diagnosed with AD with Parkinsonism. Methods: Due to the pathological overlap of between different neurodegenerative diseases, we performed a complex genetic profiling analysis by next generation sequencing (NGS) for 50 causative or risk factor genes. In silico studies and 3D modeling were also performed for the mutations. Results: We discovered a novel PSEN1 variant, G417A, located in the exon 12 in the 8 transmembrane region. This mutation may impair the splicing of PSEN1 transcriptome, since it is located adjacent to the splice site. Conclusions:PolyPhen and SIFT revealed PSEN1 G417A mutation as probably damaging, and 3D protein structure prediction revealed that it may result extra stress inside the TM region due to the higher hydrophobicity of alanine. Cell studies are currently ongoing to verify the role of mutation in AD progression.