Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5738478 | Neuroscience Letters | 2017 | 7 Pages |
â¢Amyloid Precursor Protein (APP) gene.â¢APP-mRNA isoforms.â¢Lesch-Nyhan Disease.â¢Neurodevelopmenatal and Neurodegenerative Disorders.
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 624Â bp, with a deletion starting after 49Â bp of the 5â² end of exon 3 followed by a complete deletion of exons 4-15, mutations in exon 1: c.22CÂ >Â T, p.L18F, and exon 3: c.269AÂ >Â G, p.Q90R encoding APP207 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.