Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Neurobiol Aging. 2019 Dec;84:238.e1-238.e4. doi: 10.1016/j.neurobiolaging.2019.05.014. Epub 2019 Jun 13.
"Presenilin 1" (PSEN1) gene mutations are the major known genetic cause of early-onset Alzheimer's disease. Herein, we report a novel heterozygous PSEN1 mutation (p.Leu424Pro) in a Turkish patient presenting with deterioration of short-term memory and visuospatial skills starting at the age of 47 years. This novel mutation is located in the conserved residue of transmembrane domain 8 coded by exon 12. At the protein level, this mutation caused a disruption in the alpha helix structure of PSEN1. The structural and possible functional consequences of the mutation suggest that it has probably a pathogenic effect, which in turns had a potential role in the development of Alzheimer's disease in our patient.
“早老素 1 基因”（PSEN1）突变是早发性阿尔茨海默病的主要已知遗传原因。在此，我们报告了一名土耳其患者的新型杂合 PSEN1 突变（p.Leu424Pro），该患者从 47 岁开始出现短期记忆和视空间技能恶化。该新型突变位于外显子 12 编码的跨膜域 8 的保守残基中。在蛋白质水平上，该突变导致 PSEN1 的α螺旋结构中断。该突变的结构和可能的功能后果表明，它可能具有致病性作用，从而可能在我们患者的阿尔茨海默病发展中发挥作用。
