4.6 Article

Identification of Novel Mutations by Targeted NGS Panel in Patients with Hyperferritinemia

期刊

GENES
卷 12, 期 11, 页码 -

出版社

MDPI
DOI: 10.3390/genes12111778

关键词

ferroportin; transferrin receptor 2; hepcidin; hemojuvelin; next generation sequencing; hemochromatosis; ferritin; iron overload

资金

  1. Association for the Study of Hemochromatosis and Iron overload Disorders-ONLUS, Monza

向作者/读者索取更多资源

This study utilized NGS technology to conduct genetic testing in patients with non-HFE-related hyperferritinemia, identifying several novel mutations. The results support the use of NGS panels in tertiary centers for iron metabolism disorders, but a portion of patients did not have identifiable genetic variants, suggesting the need for further research on other genetic defects or gene-gene and gene-environment interactions.
Background. Several inherited diseases cause hyperferritinemia with or without iron overload. Differential diagnosis is complex and requires an extensive work-up. Currently, a clinical-guided approach to genetic tests is performed based on gene-by-gene sequencing. Although reasonable, this approach is expensive and time-consuming and Next Generation Sequencing (NGS) technology may provide cheaper and quicker large-scale DNA sequencing. Methods. We analysed 36 patients with non-HFE-related hyperferritinemia. Liver iron concentration was measured in 33 by magnetic resonance. A panel of 25 iron related genes was designed using SureDesign software. Custom libraries were generated and then sequenced using Ion Torrent PGM. Results. We identified six novel mutations in SLC40A1, three novel and one known mutation in TFR2, one known mutation and a de-novo deletion in HJV, and a novel mutation in HAMP in ten patients. In silico analyses supported the pathogenic role of the mutations. Conclusions. Our results support the use of an NGS-based panel in selected patients with hyperferritinemia in a tertiary center for iron metabolism disorders. However, 26 out of 36 patients did not show genetic variants that can individually explain hyperferritinemia and/or iron overload suggesting the existence of other genetic defects or gene-gene and gene-environment interactions needing further studies.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据