Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease

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• 作者：Imelda S. Barber^a ; Jennyfer M. Garcí ; a-Cá ; rdenas^a ; Chidchanok Sakdapanichkul^a ; Christopher Deacon^a ; Gabriela Zapata Erazo^a ; Rita Guerreiro^b ; Jose Bras^b ; Dena Hernandez^c ; Andrew Singleton^c ; Tamar Guetta-Baranes^a ; Anne Braae^a ; Naomi Clement^a ; Tulsi Patel^a ; Keeley Brookes^a ; Christopher Medway^a ; Sally Chappell^a ; David M. Mann^d ; ARUK Consortium ; Peter Passmore ; David Craig ; Janet Johnston ; Bernadette McGuinness ; Stephen Todd ; Reinhard Heun ; Heike Kö ; lsch ; Patrick G. Kehoe ; Emma R.L.C. Vardy ; Nigel M. Hooper ; Stuart Pickering-Brown ; Julie Snowden ; Anna Richardson ; Matt Jones ; David Neary ; Jenny Harris ; Christopher Medway ; James Lowe ; A. David Smith ; Gordon Wilcock ; Donald Warden ; Clive Holmes
• 关键词：Alzheimer's disease ; Early-onset ; Sporadic ; Screening ; APP ; rs367709245
• 刊名：Neurobiology of Aging
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：39
• 期：Complete
• 页码：220.e1-220.e7
• 全文大小：902 K

文摘

Early-onset Alzheimer's disease (EOAD) can be familial (FAD) or sporadic EOAD (sEOAD); both have a disease onset ≤65 years of age. A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. Four samples were shown to be heterozygous for 1 of 3 known causative mutations: p.A713T, p.V717I, and p.V717G; this highlights the importance of screening EOAD patients for causative mutations. Additionally, we document an intronic 6 base pair (bp) deletion located 83 bp downstream of exon 17 (rs367709245, IVS17 83-88delAAGTAT), which has a nonsignificantly increased minor allele frequency in our sEOAD cohort (0.006) compared to LOAD (0.002) and controls (0.002). To assess the effect of the 6-bp deletion on splicing, COS-7 and BE(2)-C cells were transfected with a minigene vector encompassing exon 17. There was no change in splicing of exon 17 from constructs containing either wild type or deletion inserts. Sequencing of cDNA generated from cerebellum and temporal cortex of a patient harboring the deletion found no evidence of transcripts with exon 17 removed.