Next-generation sequencing: Application of a novel platform to analyze atypical iron disorders
McDonald, C.J., Ostini, L., Wallace, D.F., Lyons, A., Crawford, D.H.G., & Subramaniam, V.N. (2015) Next-generation sequencing: Application of a novel platform to analyze atypical iron disorders. Journal of Hepatology, 63(5), pp. 1288-1293.
The development of targeted next-generation sequencing (NGS) applications now promises to be a clinically viable option for the diagnosis of rare disorders. This approach is proving to have significant utility where standardized testing has failed to identify the underlying molecular basis of disease. We have developed a unique targeted NGS panel for the systematic sequence-based analysis of atypical iron disorders. We report the analysis of 39 genes associated with iron regulation in eight cases of atypical iron dysregulation, in which five cases we identified the definitive causative mutation, and a possible causative mutation in a sixth. We further provide a molecular and cellular characterization study of one of these mutations (TFR2, p.I529N) in a familial case as proof of principle. Cellular analysis of the mutant protein indicates that this amino acid substitution affects the localization of the protein, which results in its retention in the endoplasmic reticulum and thus failure to function at the cell surface. Our unique NGS panel presents a rapid and cost-efficient approach to identify the underlying genetic cause in cases of atypical iron homeostasis disorders.
Impact and interest:
Citation counts are sourced monthly from and citation databases.
These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.
Citations counts from theindexing service can be viewed at the linked Google Scholar™ search.
|Item Type:||Journal Article|
|Keywords:||adult; aged; amino acid substitution; Article; cell surface; cellular distribution; clinical article; cost effectiveness analysis; endoplasmic reticulum; female; gene mutation; genetic analysis; human; iron overload; loss of function mutation; male; middl, calnexin; hemojuvelin; hephaestin; hephaestin like 1; transferrin receptor 2; unclassified drug|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
|Copyright Owner:||© 2015 European Association for the Study of the Liver|
|Deposited On:||12 Oct 2016 02:17|
|Last Modified:||14 Oct 2016 04:17|
Repository Staff Only: item control page