Erken Başalayan Alzheimer Hastalığında PSEN1 ve APP Gen Mutasyonlarının Araştırılması

Abstract

Alzheimer’s disease (AD) accounts approximately 60% of all dementia cases. Although neuropathological features are common in both early onset(age <65) and late onset (age >65) forms, intermittently atypical clinical courses and indications can be observed in early onset patients.Lifetime risk for developing the disease is reported to be 10 to 12%. In general, the risk for the first degree relatives is found 2.5 times higherthan in controls. Early onset forms account 1-6% of the AD, and 60% of this group underlies the familial forms. 13% of the familial forms displayautosomal dominant (OD) inheritance. Presently, mutations in three different genes are associated with OD form and mutation frequency of thesegenes in all AD cases is 5 - 10%. 20 - 70% of the determined mutations are found in PSEN1 and 10 – 15% are found in APP gene while PSEN2gene mutations are reported to be very rare. The studies show that e4 allele contributes to clinical diagnosis and risk status of the disease, thoughit is neither specific nor sensitive for presymptomatic diagnosis. Genome wide association studies show 21 further loci related to the disease.In our study, total of 59 early onset AD cases, 30 familial in which one atypical, and 29 isolated in which four atypical AD, referred to Departmentof Medical Genetics from Neurology Department of Istanbul Medical Faculty, between the years of 2013 – 2015, screened for coding exons ofPSEN1, exon 16-17 of APP, and exon 4 of APOE genes by Sanger sequencing method. Four of the cases found to carry AD associated PSEN1gene mutations (6.7%), and one found to carry APOE-e4 homozygosity (1.7 %) in the group.Acknowledgement about the associated genetic mutations in early onset AD provides additional diagnostic benefit for the genetic counseling ofthe families. Genetic heterogeneity and unfavorable environmental factors cause molecular diagnosis challenging. Next generation sequencingtechnology, will grant screening of many associated genes in compact, quick, and cost effective manner, and besides will underlie the role ofgenetic factors more efficiently.