Vaula G, Mortilla M, Tupler R, Lukiw W, Tanzi R, Nee L, Polinsky R, Foncin J F, Bruni A C, Montesi M P
Department of Medicine and Neurology, Faculty of Medicine, University of Toronto, Ont., Canada.
Neurosci Lett. 1992 Sep 14;144(1-2):46-8. doi: 10.1016/0304-3940(92)90712-g.
Mutations in the beta-amyloid precursor protein (APP) gene have been associated with both familial Alzheimer disease (FAD) and with hereditary cerebral haemorrhage. The polymerase chain reaction was used to both amplify and sequence exon 4 of the APP gene from genomic DNA of subjects with FAD and normal control subjects. A novel, rare, conservative DNA sequence variant was discovered at nucleotide 459 of codon 153 (valine) in exon 4 of the APP gene in an affected member of a large FAD pedigree. Segregation studies indicate that this mutation is likely to be non-pathogenic, but must be recognized and discriminated from pathogenic mutations during sequencing studies of the APP gene in patients with FAD.
β-淀粉样前体蛋白（APP）基因突变与家族性阿尔茨海默病（FAD）和遗传性脑出血均有关联。采用聚合酶链反应从FAD患者及正常对照者的基因组DNA中扩增并测序APP基因的第4外显子。在一个大型FAD家系的一名患病成员中，于APP基因第4外显子密码子153（缬氨酸）的第459位核苷酸处发现了一种新的、罕见的、保守的DNA序列变异。分离研究表明，该突变可能无致病性，但在对FAD患者进行APP基因测序研究时，必须识别并与致病性突变区分开来。
