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

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...

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Autores principales:	Giulia Ravasi, Sara Pelucchi, Francesca Bertola, Martina Maria Capelletti, Raffaella Mariani, Alberto Piperno
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ferroportin transferrin receptor 2 hepcidin hemojuvelin next generation sequencing hemochromatosis Genetics QH426-470
Acceso en línea:	https://doaj.org/article/e38685ca5f954ce69e9b25c24410c721
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spelling	oai:doaj.org-article:e38685ca5f954ce69e9b25c24410c7212021-11-25T17:41:51ZIdentification of Novel Mutations by Targeted NGS Panel in Patients with Hyperferritinemia10.3390/genes121117782073-4425https://doaj.org/article/e38685ca5f954ce69e9b25c24410c7212021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1778https://doaj.org/toc/2073-4425Background. 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-<i>HFE</i>-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 <i>SLC40A1</i>, three novel and one known mutation in <i>TFR2</i>, one known mutation and a de-novo deletion in <i>HJV</i>, and a novel mutation in <i>HAMP</i> 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.Giulia RavasiSara PelucchiFrancesca BertolaMartina Maria CapellettiRaffaella MarianiAlberto PipernoMDPI AGarticleferroportintransferrin receptor 2hepcidinhemojuvelinnext generation sequencinghemochromatosisGeneticsQH426-470ENGenes, Vol 12, Iss 1778, p 1778 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ferroportin transferrin receptor 2 hepcidin hemojuvelin next generation sequencing hemochromatosis Genetics QH426-470
spellingShingle	ferroportin transferrin receptor 2 hepcidin hemojuvelin next generation sequencing hemochromatosis Genetics QH426-470 Giulia Ravasi Sara Pelucchi Francesca Bertola Martina Maria Capelletti Raffaella Mariani Alberto Piperno Identification of Novel Mutations by Targeted NGS Panel in Patients with Hyperferritinemia
description	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-<i>HFE</i>-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 <i>SLC40A1</i>, three novel and one known mutation in <i>TFR2</i>, one known mutation and a de-novo deletion in <i>HJV</i>, and a novel mutation in <i>HAMP</i> 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.
format	article
author	Giulia Ravasi Sara Pelucchi Francesca Bertola Martina Maria Capelletti Raffaella Mariani Alberto Piperno
author_facet	Giulia Ravasi Sara Pelucchi Francesca Bertola Martina Maria Capelletti Raffaella Mariani Alberto Piperno
author_sort	Giulia Ravasi
title	Identification of Novel Mutations by Targeted NGS Panel in Patients with Hyperferritinemia
title_short	Identification of Novel Mutations by Targeted NGS Panel in Patients with Hyperferritinemia
title_full	Identification of Novel Mutations by Targeted NGS Panel in Patients with Hyperferritinemia
title_fullStr	Identification of Novel Mutations by Targeted NGS Panel in Patients with Hyperferritinemia
title_full_unstemmed	Identification of Novel Mutations by Targeted NGS Panel in Patients with Hyperferritinemia
title_sort	identification of novel mutations by targeted ngs panel in patients with hyperferritinemia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e38685ca5f954ce69e9b25c24410c721
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_version_	1718412137010823168

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

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