BackgroundWilson disease (WD) is an autosomal recessive disorder. The WD gene, ATP7B, encodes a copper-transporting ATPase involved in the transport of copper into the plasma protein ceruloplasmin and in excretion of copper from the liver. ATP7B mutations cause copper to accumulate in the liver and brain.ObjectivesWe examined the ATP7B mutation spectrum in Wilson disease patients in Iran.Patients and MethodsGenomic DNA was extracted from patients with Wilson disease. The entire coding region of the ATP7B gene was amplified using PCR and analyzed using direct sequencing.ResultsWe identified five novel mutations in 5 Iranian patients with Wilson disease. The first was a transversion, c.2363C > T, which led to an amino acid change from threonine to isoleucine. The second mutation was a deletion, c.2532delA (Val845Ser), which occurred in exon 10. The third mutation was a transition mutation, c.2311C > G (Leu770Leu), which occurred in the TM4 domain of the ATP7B protein. The fourth mutation was a transversion, (c.3061G > A) (Lys1020Lys), in exon 14. Lastly, we identified a transversion, c.3206C > A (His1069Asn) in exon 14 which led to a change in function of the ATP loop domain of the ATP7B protein. The H1069Q mutation was identified as the most common mutation in our study population.ConclusionsBased on our findings, the H1069Q may be a biomarker that can be used in a rapid detection assay for diagnosing WD patients
Background: Wilson disease (WD) is an autosomal recessive disorder. The WD gene, ATP7B, encodes a copper-transporting ATPase involved in the transport of copper into the plasma protein ceruloplasmin and in excretion of copper from the liver. ATP7B mutations cause copper to accumulate in the liver and brain. Objectives: We examined the ATP7B mutation spectrum in Wilson disease patients in Iran. Patients and Methods: Genomic DNA was extracted from patients with Wilson disease. The entire coding region of the ATP7B gene was amplified using PCR and analyzed using direct sequencing. Results: We identified five novel mutations in 5 Iranian patients with Wilson disease. The first was a transversion, c.2363C > T, which led to an amino acid change from threonine to isoleucine. The second mutation was a deletion, c.2532delA (Val845Ser), which occurred in exon 10. The third mutation was a transition mutation, c.2311C > G (Leu770Leu), which occurred in the TM4 domain of the ATP7B protein. The fourth mutation was a transversion, (c.3061G > A) (Lys1020Lys), in exon 14. Lastly, we identified a transversion, c.3206C > A (His1069Asn) in exon 14 which led to a change in function of the ATP loop domain of the ATP7B protein. The H1069Q mutation was identified as the most common mutation in our study population. Conclusions: Based on our findings, the H1069Q may be a biomarker that can be used in a rapid detection assay for diagnosing WD patients.
Factors that underlie the association of diverse traits of the metabolic syndrome have remained largely unknown. The strong heritable nature of this condition provides an exceptional avenue for discovery of the disease mechanisms by using modern techniques of human molecular genetics. Strikingly, efforts by genome-wide association studies to identify common variants that show association with two or more traits have largely failed. Growing evidence indicates excess of rare genetic variants through recent exponential population growth, raising the possibility for their causal role in common diseases. With the advent of high throughput sequencing the power for identification of functional rare variants has dramatically increased. By biasing for extreme phenotypes and utilizing traditional method of segregation analysis we have discovered a number of disease genes for metabolic syndrome and coronary artery disease. A major benefit of this strategy is that true causal relationships has been established between rare variations in a gene, its cognate pathways and the disease of interest. These, in turn, have provided fundamental new insight into pathogenesis of poorly understood diseases such as plaque erosion, and logical starting points for identifying new targets and pathways for therapeutic intervention. By dissecting cognate pathways, we have identified novel targets, including Dyrk1B kinase, a novel incretin and components of Wnt signaling pathway to treat CAD, diabetes and hyperlipidemia and have implemented those succesfuly in animal models.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.