Next-generation sequencing of hereditary hemochromatosis-related genes: Novel likely pathogenic variants found in the Portuguese population

Ricardo A M Faria, Bruno Silva, Catarina Oliveira Silva, Pedro Loureiro, Ana Queiroz, Sofia Fraga, Jorge Esteves, Diana Mendes, Rita Fleming, Luís Vieira, João Gonçalves, Paula Faustino

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1GtextgreaterC)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5'-UTR of HAMP gene (c-25GtextgreaterA). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders. (C) 2016 Elsevier Inc All rights reserved.
Original languageEnglish
Pages (from-to)10-15
Number of pages6
JournalBlood Cells Molecules And Diseases
Volume61
DOIs
Publication statusPublished - Oct 2016

Keywords

  • Iron metabolism
  • Hereditary hemochromatosis
  • Next-generation sequencing
  • Novel mutations
  • Genetic variants

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