A novel variant c.3706C>T p.(Avg 1236Cys) in the <i>ABCA7</i> gene in a Saudi patient with susceptibility to Alzheimer's disease 9

Abstract

Alzheimer's disease (AD) is the most common cause of dementia with around 50 million people suffering from this disease worldwide. Mutations in the ATP-binding cassette sub-family A member 7 (ABCA7) have been reported to cause susceptibility to AD 9 (OMIM #608907). In this study, we report a novel variant in ABCA7 in a Saudi patient with susceptibility to AD 9 and a strong family history of neurodegenerative disorders, which may be explained by the same variant. We studied a single 57-year-old female patient with typical symptoms of AD supported by MRI findings from a Saudi family with a positive history of a similar disease in multiple individuals. The case study was conducted in King Abdulaziz Medical City in Jeddah, Saudi Arabia. Whole-exome sequencing identified the novel heterozygous variant c.3706C>T p.(Avg 1236Cys) in the ABCA7 gene, which leads to an amino acid exchange. Furthermore, bioinformatics in silico programs predict a pathogenic effect for this variant. To the best of our knowledge, the variant has not been described in the literature so far as evidenced by a thorough literature review using multiple databases such as Ovid, Medline, EMBASE, ProQuest, Science Direct, Google Scholar, and PubMed. In this article, we reported a middle-aged Saudi woman with a novel variant in ABCA7 who had clinical features of both AD and Parkinson's disease. Given the reported function of this gene, it is most likely that it is etiological and pathological because of the presenting complex neurological disease due to decreased clearance of β-amyloid and α-Synuclein. We illustrate the importance of this interesting gene that could be implicated in several neurodegenerative disorders.

Genetic Phenotypes of Alzheimer’s Disease: Mechanisms and Potential Therapy

“…The rs143718918 variant causes a missense mutation, and the rs538591288 deletion causes a frameshift mutation of ABCA7 (May et al 2018 ). ABCA7 heterozygous variant c.3706C > T p.(Avg 1236Cys) was found in seven affected members in a Saudi family, which is likely pathogenic because of the presenting complex neurological disease due to decreased clearance of Aβ and α-synuclein (Algahtani et al 2020 ). Missense variants in ABCA7 (P143S and A1507T) were significantly associated with FAD when compared with the East Asian controls in the ExAC database (Zhang et al 2020b ).…”