Mutational analysis in familial Alzheimer’s disease of Han Chinese in Taiwan with a predominant mutation PSEN1 p.Met146Ile
Autor: | Chen-Jee Hong, Chih-Ya Cheng, Yung-Shuan Lin, Yi-Chu Liao, Jong Ling Fuh |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty DNA Mutational Analysis Taiwan lcsh:Medicine Disease medicine.disease_cause Article 03 medical and health sciences Amyloid beta-Protein Precursor 0302 clinical medicine Alzheimer Disease Internal medicine PSEN2 Presenilin-2 PSEN1 Genetics Presenilin-1 Medicine Humans Family history lcsh:Science Retrospective Studies Mutation Multidisciplinary business.industry lcsh:R Retrospective cohort study Middle Aged Hyperintensity 030104 developmental biology Neurology Cohort Female lcsh:Q business 030217 neurology & neurosurgery Neuroscience |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-9 (2020) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Mutations in PSEN1, PSEN2, or APP genes are known to be causative for autosomal dominant Alzheimer’s disease (ADAD). While more than 400 mutations were reported worldwide, predominantly PSEN1, over 40 mutations have been reported in Han Chinese and were associated with earlier onset and more affected family members. Between 2002 and 2018, 77 patients in the neurological clinic of Taipei Veterans General Hospital with a history suggestive of ADAD were referred for mutational analysis. We retrospectively collected demographics, initial symptoms, neurological features and inheritance. We identified 16 patients with PSEN1 and 1 with APP mutation. Among the mutations identified, PSEN1 p.Pro117Leu, p.Met146Ile, p.Gly206Asp, p.Gly209Glu, p.Glu280Lys and p.Leu286Val and APP p.Asp678His were known pathogenic mutations; PSEN1 p.His131Arg and p.Arg157Ser were classified as likely pathogenic and variance of unknown significance respectively. The mean age at onset was 46.2 ± 6.2 years in patients with mutation found. PSEN1 p.Met146Ile, occurred in 56.2% (9/16) of patients with PSEN1 mutations, was the most frequent mutation in the cohort. The additional neurological features occurring in 9 PSEN1 p.Met146Ile index patients were similar with the literature. We found patients with genetic diagnoses were more likely to have positive family history, younger age at onset and less brain white matter hyperintensity. |
Databáze: | OpenAIRE |
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