The R278I Mutation of PSEN1 in the Familial Alzheimer Disease

Abstract

Familial Alzheimer disease (AD) is caused by mutations in the PSEN1, PSEN2 and APP genes. In rare cases, mutations in ABCA7 and SORL1 also show familial AD, depending on their positions in the proteins. 1,2 About 5% of early onset AD (EOAD) are caused by mutations of these 5 genes. 3 The clues about having causal gene mutations in EOAD are the age of onset and number of EOAD patients in their families. If EOAD patients have one or more relatives with EOAD, 77% of their families have the causal gene mutations. 4 In sporadic cases, the causal gene can be identified at a very low rate of 17.9% for patients of age at onset under 50 and 1.2% for those over 50. 4 Familial EOAD cases have been reported due to a loss of function mutations that seriously alter the function of the ABCA7 gene. 2 The mutations in genes other than ABCA7 make it difficult to determine pathogenicity. In this letter, we report a case of the R278I mutation in PSEN1, which has not been reported in Korean familial EOAD patients. A 49-year-old man visited our dementia center complaining of memory impairments. According to the patient's report, he felt mild forgetfulness for about 10 years. In 2018, he began to easily forget the stories that he heard. Sometimes, he could not remember what he had done at work. When he talked with friends, he often could not remember the important previous events. His friends advised him to visit clinics. As a computer programmer, there is no problem in working. Driving, money management, hobbies and social relations are maintained as before. No neurological findings were observed. According to neuropsychological tests, his clinical diagnosis was multiple domain amnestic mild cognitive impairment (MCI). He remembered that his father had dementia in his early sixties, and his brother also developed dementia in his early fifties. His mother has still normal cognition to date. The patient has 2 sisters who are 58 and 55 years old, and neither of them have ever complained of memory impairment (Fig. 1). No atrophy was observed on magnetic Dement Neurocogn Disord. 2020 Mar;19(1):33-35 https://doi.