A neurodevelopmental disorder with a nonsense mutation in the Ox-2 antigen domain of the amyloid precursor protein (APP) gene. (4th May 2017)

• Record Type: Journal Article
• Authors: Nguyen, Khue Vu; Leydiker, Karen; Wang, Raymond; Abdenur, Jose; Nyhan, William L.
• Is Part Of: Nucleosides, nucleotides & nucleic acids. Volume 36:Number 5(2017)
• Page Start: 317
• Page End: 327
• Publication Date: 2017-05-04
• Subjects: Kinetic method -- RT-PCR technique -- sequencing -- amyloid precursor protein -- nonsense mutation in the Ox-2 antigen domain -- epigenetics -- neurodevelopmental disorder; Nucleosides -- Periodicals; Nucleotides -- Periodicals; Nucleic acids -- Periodicals; 572.8
• DOI: 10.1080/15257770.2016.1267361
• Languages: English
• ISSNs: 1525-7770

Abstract

ABSTRACT: We report a patient, an infant with a neurodevelopmental disorder manifesting intractable complex partial epilepsy, bull's eye maculopathy, microcephaly, bilateral cataracts, truncal hypotonia, and spasticity of all four extremities. Sequencing of genomic DNA revealed mutations in (a) exon 8 (Ox-2 antigen domain) of the amyloid precursor protein (APP) gene: c.1075C>T, p.Arg359 * (b) exon 8 of the senataxin (SETX) gene: c.4738C>T, p.Arg1580Cys, and (c) exon 2 of the ceroid-lipofuscinosis, neuronal 8 (CLN8) gene: c.685C>G, p.Pro229Ala. Using a quantitative method for measurement of various APP-mRNA isoforms, we found that the APP-mRNA isoform of 624 bp with a deletion starting after 49 bp 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 APP207 isoform was the most abundant one, and would appear to be responsible for the clinical manifestations. This is the first example that may underline the role of the epigenetic regulation in the expression of APP gene leading to a neurodevelopmental disorder resulting from a nonsense mutation in the Ox-2 antigen domain.