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.

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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.

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ID Code: 99754
Item Type: Journal Article
Refereed: Yes
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
DOI: 10.1016/j.jhep.2015.06.027
ISSN: 0168-8278
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

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