Clinical and genetic analysis of a pedigree of a thirty-six-year-old Familial Alzheimer's disease patient

Hong, Kyung Sue; Kim, S. Peter; Na, Duk L.; Kim, Jae Gyeong; Suh, Yeon‐Lim; Kim, Sang Eun; Kim, Jong-Won

doi:10.1016/s0006-3223(97)00347-8

Cited by 8 publications

(6 citation statements)

References 12 publications

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“… 12 , 23 , 41 , 88 PSEN1 H163R, the most frequently described AD causative mutation among French, German, and Turkish Caucasians, has appeared in Korea and Japan. 22 , 47 , 53 , 69 Additional mutations, such as Leu226Phe, Thr116Ile, Met233Thr (Korea), Ile143Thr, and Arg269His (Japan), were also reported in Korea and Japan. 16 , 17 , 27 , 28 , 55 , 66 – 68 In the People’s Republic of China, most of the PSEN1 variants, such as Ile167del, Ser169del, and Leu248Pro, were newly discovered.…”

Section: Discussionmentioning

confidence: 99%

“…In Korea, Hong et al described the mutation in a female patient who was hospitalized because of memory disturbances and personality changes at the age of 36 years. 22 Symptoms started in her late 20s. Strong family history of disease was observed in her family; of the 22 family members tested, nine members were affected.…”

Section: App Psen1 and Psenmentioning

confidence: 99%

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Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Bagyinszky

Youn

et al. 2016

CIA

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Alzheimer’s disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People’s Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People’s Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.

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Section: Discussionmentioning

confidence: 99%

Section: App Psen1 and Psenmentioning

confidence: 99%

Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Bagyinszky

Youn

et al. 2016

CIA

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“…In 1996, Hong et al published a case report on PSEN1 H163R in a Korean family with EOAD, which is a quite common causative mutation for AD 27. In 2008, Park et al published a genetic screening study, but they employed only 6 EOAD patients.…”

Section: Discussionmentioning

confidence: 99%

A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

An¹,

Park²,

Bagyinszky³

et al. 2016

CIA

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Early-onset Alzheimer’s disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16–17), PSEN1 (exons 3–12), and PSEN2 (exons 3–12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We suggest early AD onset and not carrying APOE ε4 allele are more reliable factors for predicting an induced genetic mutation than the presence of the family history in Korean EOAD population.

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“…In Korea, there was only one report of genetically confirmed case of EOAD (15). However, although the number of study subjects was small, this study shows that PSEN1 or APP gene mutations exist in other Korean patients with EOAD and few reports on the EOAD patients confirmed by genetic analysis might be due to under-utilization of genetic tests.…”

Section: Discussionmentioning

confidence: 99%

“…In the Korean population, there has been only a single report on a mutation in the PSEN1 gene in a pedigree of a 36-yr-old familial AD (15). In this study, mutation analysis of the APP , PSEN1 , and PSEN2 genes was performed to determine the contribution of these genes in the genetic background of EOAD patients in Korea.…”

Section: Introductionmentioning

confidence: 99%

Identification of PSEN1 and APP Gene Mutations in Korean Patients with Early-Onset Alzheimer's Disease

Park

Lee

et al. 2008

J Korean Med Sci

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Although mutations in three genes, amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2), have been identified as genetic causes of early-onset Alzheimer's disease (EOAD), there has been a single report on a PSEN1 mutation in Koreans. In the present study, we performed a genetic analysis of six Korean patients with EOAD. Direct sequencing analysis of the APP, PSEN1 and PSEN2 genes revealed two different mutations of the PSEN1 gene (G206S and M233T) and one mutation of the APP gene (V715M) in three patients with age-at-onset of 34, 35, and 42 yr, respectively. In addition, two patients with age-at-onset of 55 and 62 yr, respectively, were homozygous for APOE ε4 allele. One woman had no genetic alterations. These findings suggest that PSEN1 and APP gene mutations may not be uncommon in Korean patients with EOAD and that genetic analysis should be provided to EOAD patients not only for the identification of their genetic causes but also for the appropriate genetic counseling.

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Clinical and genetic analysis of a pedigree of a thirty-six-year-old Familial Alzheimer's disease patient

Cited by 8 publications

References 12 publications

Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

Identification of PSEN1 and APP Gene Mutations in Korean Patients with Early-Onset Alzheimer's Disease

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Clinical and genetic analysis of a pedigree of a thirty-six-year-old Familial Alzheimer's disease patient

Cited by 8 publications

References 12 publications

Mutations, associated with early-onset Alzheimer&rsquo;s disease, discovered in Asian countries

Mutations, associated with early-onset Alzheimer&rsquo;s disease, discovered in Asian countries

A genetic screen of the mutations in the Korean patients with early-onset Alzheimer&rsquo;s disease

Identification of PSEN1 and APP Gene Mutations in Korean Patients with Early-Onset Alzheimer's Disease

Contact Info

Product

Resources

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Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease