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ACE gene missense mutation in a case with early-onset, rapid progressing dementia.

ABSTRACT: The population of early-onset Alzheimer's disease (EOAD) accounts for 1%-2% of the total population of Alzheimer's disease, and genetic mutations are more common in EOAD. The first symptom of the patient in the present case report was the decline in memories of recent events, and the disease progressed rapidly in the following 2?years. Genetic testing has revealed the presence of genetic mutations (c.A479G, p.N160S) of ACE, which causes the 160th codon of the ACE protein to change from aspartic acid to serine, and at the same time genotype of apolipoprotein E (APOE) is ?3/?4. We think that this patient carries the mutation type of the sensitive gene ACE and the risk gene APOE of Alzheimer's disease, and this is the reason why the disease progressed rapidly. Moreover, we discussed ACE genetic mutation's meaning in EOAD progression.

SUBMITTER: Ni J

PROVIDER: S-EPMC6802971 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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ACE gene missense mutation in a case with early-onset, rapid progressing dementia.

Ni Jing J Xiao Shifu S Li Xia X Sun Lin L

General psychiatry 20191008 5

The population of early-onset Alzheimer's disease (EOAD) accounts for 1%-2% of the total population of Alzheimer's disease, and genetic mutations are more common in EOAD. The first symptom of the patient in the present case report was the decline in memories of recent events, and the disease progressed rapidly in the following 2 years. Genetic testing has revealed the presence of genetic mutations (c.A479G, p.N160S) of ACE, which causes the 160th codon of the ACE protein to change from aspartic ...[more]

PMID: 31673674

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Project description:There could be an overlap of monogenic diabetes and early-onset type 2 diabetes mellitus. Precise diagnosis of early-onset diabetes has proven valuable for understanding the mechanism of diabetes and selecting optimal therapy. The majority of maturity onset diabetes of the young (MODY) pathogenic genes in China is still unknown. In this study, a family with suspected MODY was enrolled. Whole-exome sequencing (WES) was used to analyze the variants of the proband. Variants were filtered according to their frequency, location, functional consequences, and bioinformatics software. Candidate pathogenic variants were validated by Sanger sequencing and tested for cosegregation in other members of the family and nonrelated healthy controls. KEGG (Kyoto Encyclopedia of Genes and Genomes) and PPI (protein-protein interaction) analysis were conducted using the DAVID (Database for Annotation, Visualization, and Integrated Discovery) and the STRING online analysis tools for the candidate pathogenic gene. A total of 123291 variants including 105344 SNPs and 17947 InDels were found in WES. A likely pathogenic rare missense heterozygous mutation in diabetes genes (c.2137C > T, p.His713Tyr in IRS1) was identified, which was a cosegregate in this family and not in nonrelated healthy controls. The position of the mutation in the aminoacid sequence of the gene is highly conserved among the species. 2 significantly enriched KEGG pathways were identified including bta04930, type II diabetes mellitus (GCK, INS, PDX1, ABCC8, and IRS1), and bta04910, insulin signaling pathway (GCK, INS, and IRS1). PPI analysis displayed that IRS1 interacts with 3 known pathogenic proteins including INS, KCNJ11, and GCK. We conclude that WES could be an initial option for genetic testing in patients with early-onset diabetes. IRS1 p.His713Tyr is implicated as a possible pathogenic mutation in monogenic diabetes, which might require further validation, and the precise molecular mechanism underlying the influence of IRS1 p.His713Tyr on the development of diabetes remains to be determined in the further prospective studies.

Dataset Information

ACE gene missense mutation in a case with early-onset, rapid progressing dementia.

Publications

ACE gene missense mutation in a case with early-onset, rapid progressing dementia.

Similar Datasets

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