PMID- 28192196
OWN - NLM
STAT- MEDLINE
DCOM- 20171219
LR  - 20180824
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 643
DP  - 2017 Mar 16
TI  - Quantification of various APP-mRNA isoforms and epistasis in Lesch-Nyhan disease.
PG  - 52-58
LID - S0304-3940(17)30122-2 [pii]
LID - 10.1016/j.neulet.2017.02.016 [doi]
AB  - The present work is the development of a simple and specific kinetic method based 
      on RT-PCR technique coupled with direct sequencing for quantification of various 
      amyloid precursor protein-mRNA isoforms (APP-mRNA isoforms) in biological 
      samples, especially for identifying the most abundant one that may decisive for 
      the normal status or disease risk. Application of this kinetic method to the 
      Lesch-Nyhan disease (LND) was performed and results indicated an epistasis 
      between mutated hypoxanthine phosphoribosyltransferase1 (HPRT1) and APP genes. 
      APP-mRNA isoform of 624bp, with a deletion starting after 49bp of the 5' end of 
      exon 3 followed by a complete deletion of exons 4-15, mutations in exon 1: 
      c.22C>T, p.L18F, and exon 3: c.269A>G, p.Q90R encoding APP(207) isoform, was the 
      most abundant one in most of the LND patients and would be responsible for the 
      neurobehavioral syndrome in these patients. The method is useful for identifying 
      the defective APP-mRNA isoform in LND patients, and in neurodevelopmental and 
      neurodegenerative disorders in which the APP gene is involved in the pathogenesis 
      of diseases such as autism, fragile X syndrome, amyotrophic lateral sclerosis, 
      and Alzheimer's disease, and may pave the way for new strategies applicable to 
      rational antisense drugs design.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Nguyen, Khue Vu
AU  - Nguyen KV
AD  - Department of Medicine, Biochemical Genetics and Metabolism, The Mitochondrial 
      and Metabolic Disease Center, School of Medicine, University of California, San 
      Diego, Building CTF, Room C-103, 214 Dickinson Street, San Diego, CA, 92103-8467, 
      USA; Department of Pediatrics, University of California, San Diego, School of 
      Medicine, San Diego, La Jolla, CA, 92093, USA. Electronic address: 
      kvn006@ucsd.edu.
FAU - Nyhan, William L
AU  - Nyhan WL
AD  - Department of Pediatrics, University of California, San Diego, School of 
      Medicine, San Diego, La Jolla, CA, 92093, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170210
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA Isoforms)
RN  - EC 2.4.2.8 (Hypoxanthine Phosphoribosyltransferase)
SB  - IM
MH  - Alzheimer Disease/genetics
MH  - Amyloid beta-Protein Precursor/*genetics
MH  - Epistasis, Genetic/*genetics
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Hypoxanthine Phosphoribosyltransferase/genetics
MH  - Lesch-Nyhan Syndrome/*genetics
MH  - Mutation/genetics
MH  - Neurodegenerative Diseases/genetics
MH  - Protein Isoforms/genetics
MH  - RNA Isoforms/*metabolism
OTO - NOTNLM
OT  - Amyloid precursor protein
OT  - Epigenetics
OT  - Epistasis
OT  - Kinetic method
OT  - Lesch-Nyhan disease
OT  - Neurodevelopmental and neurodegenerative disorders
EDAT- 2017/02/14 06:00
MHDA- 2017/12/20 06:00
CRDT- 2017/02/14 06:00
PHST- 2016/11/22 00:00 [received]
PHST- 2017/02/01 00:00 [revised]
PHST- 2017/02/07 00:00 [accepted]
PHST- 2017/02/14 06:00 [pubmed]
PHST- 2017/12/20 06:00 [medline]
PHST- 2017/02/14 06:00 [entrez]
AID - S0304-3940(17)30122-2 [pii]
AID - 10.1016/j.neulet.2017.02.016 [doi]
PST - ppublish
SO  - Neurosci Lett. 2017 Mar 16;643:52-58. doi: 10.1016/j.neulet.2017.02.016. Epub 
      2017 Feb 10.