Besançon R, Lorenzi A, Cruts M, Radawiec S, Sturtz F, Broussolle E, Chazot G, van Broeckhoven C, Chamba G, Vandenberghe A
Laboratoire de Psychopharmacologie Biologique, Faculté de Pharmacie, Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université Claude Bernard Lyon-I, France.
Hum Mutat. 1998;11(6):481. doi: 10.1002/(SICI)1098-1004(1998)11:6<481::AID-HUMU12>3.0.CO;2-Q.
Mutations in the presenilin-1 (PS1) gene account for the majority of familial early-onset Alzheimer's disease (EOAD) cases. We screened the coding part of the PS1 gene for the present of mutations in a French family with EOAD, using single strand conformation polymorphism (SSCP) analysis. Patients in the pedigree showed a missense mutation in exon 11 of the PS1 gene involving a transition of G to A, altering glycine to glutamate at codon 378. The cosegregation of the mutation with EOAD in the family was studied by allele specific amplification, enhanced by the introduction of a mismatch at the penultimate position near the 3' primer end. The mutation has not been described before and is located within the third large cytoplasmic loop and may lead to the appearance of a short additional a-helix.
早老素-1（PS1）基因突变是大多数家族性早发型阿尔茨海默病（EOAD）病例的病因。我们采用单链构象多态性（SSCP）分析，对一个患有EOAD的法国家庭中PS1基因的编码部分进行了突变筛查。该家系中的患者在PS1基因第11外显子出现一个错义突变，即G突变为A，导致密码子378处的甘氨酸变为谷氨酸。通过等位基因特异性扩增研究了该突变与家系中EOAD的共分离情况，在3'引物末端倒数第二位引入错配增强了扩增效果。该突变此前未见报道，位于第三个大的细胞质环内，可能导致出现一个额外的短α螺旋。
