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Functional characterization of a novel non-coding mutation 'Ghent +49A>G' in the iron-responsive element of L-ferritin causing hereditary hyperferritinaemia-cataract syndrome

Stijn Van De Sompele UGent, Lucie Pécheux, Jorge Couso, Audrey Meunier, Mayka Sanchez and Elfride De Baere UGent (2017) SCIENTIFIC REPORTS. 7.
abstract
Hereditary hyperferritinaemia-cataract syndrome (HHCS) is a rare disorder usually caused by heterozygous mutations in the iron responsive element (IRE) in the 5’ untranslated region (5’UTR) of the L-ferritin gene (FTL), disturbing the binding of iron regulatory proteins (IRPs) and the post-transcriptional regulation of ferritin expression. Here, the proband of a consanguineous family displayed moderate bilateral cataracts and elevated serum ferritin in the absence of iron overload. The parents and siblings showed variable degrees of mild bilateral cataracts combined with elevated levels of circulating ferritin. Sequencing of FTL identified a novel 5’UTR mutation c.-151A>G, also named “Ghent +49A>G”. The zygosity of the mutation, occurring in homozygous and heterozygous state in the proband and other affected family members respectively, correlated well with severity of ophthalmological and hematological manifestations. The substitution is expected to impair the secondary structure of the upper IRE stem. Functional characterization of +49A>G by electrophoretic mobility shift assays demonstrated a reduced binding affinity for IRP1 compared to the wild-type IRE of FTL. Overall, we have expanded the repertoire of deleterious biallelic FTL IRE mutations in HHCS with this novel +49A>G mutation, the zygosity of which correlated well with the disease expression.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
consanguinity, disease genetics, DNA sequencing, functional genomics, genetic testing
journal title
SCIENTIFIC REPORTS
Sci. Rep.
volume
7
article number
18025
pages
10 pages
ISSN
2045-2322
DOI
10.1038/s41598-017-18326-6
language
English
UGent publication?
yes
classification
A1
copyright statement
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
id
8542419
handle
http://hdl.handle.net/1854/LU-8542419
date created
2017-12-18 17:05:21
date last changed
2018-01-05 15:30:04
@article{8542419,
  abstract     = {Hereditary hyperferritinaemia-cataract syndrome (HHCS) is a rare disorder usually caused by heterozygous mutations in the iron responsive element (IRE) in the 5{\textquoteright} untranslated region (5{\textquoteright}UTR) of the L-ferritin gene (FTL), disturbing the binding of iron regulatory proteins (IRPs) and the post-transcriptional regulation of ferritin expression. Here, the proband of a consanguineous family displayed moderate bilateral cataracts and elevated serum ferritin in the absence of iron overload. The parents and siblings showed variable degrees of mild bilateral cataracts combined with elevated levels of circulating ferritin. Sequencing of FTL identified a novel 5{\textquoteright}UTR mutation c.-151A{\textrangle}G, also named {\textquotedblleft}Ghent +49A{\textrangle}G{\textquotedblright}. The zygosity of the mutation, occurring in homozygous and heterozygous state in the proband and other affected family members respectively, correlated well with severity of ophthalmological and hematological manifestations. The substitution is expected to impair the secondary structure of the upper IRE stem. Functional characterization of +49A{\textrangle}G by electrophoretic mobility shift assays demonstrated a reduced binding affinity for IRP1 compared to the wild-type IRE of FTL. Overall, we have expanded the repertoire of deleterious biallelic FTL IRE mutations in HHCS with this novel +49A{\textrangle}G mutation, the zygosity of which correlated well with the disease expression.},
  articleno    = {18025},
  author       = {Van De Sompele, Stijn and P{\'e}cheux, Lucie and Couso, Jorge and Meunier, Audrey and Sanchez, Mayka and De Baere, Elfride},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keyword      = {consanguinity,disease genetics,DNA sequencing,functional genomics,genetic testing},
  language     = {eng},
  pages        = {10},
  title        = {Functional characterization of a novel non-coding mutation 'Ghent +49A{\textrangle}G' in the iron-responsive element of L-ferritin causing hereditary hyperferritinaemia-cataract syndrome},
  url          = {http://dx.doi.org/10.1038/s41598-017-18326-6},
  volume       = {7},
  year         = {2017},
}

Chicago
Van De Sompele, Stijn, Lucie Pécheux, Jorge Couso, Audrey Meunier, Mayka Sanchez, and Elfride De Baere. 2017. “Functional Characterization of a Novel Non-coding Mutation ‘Ghent +49A>G’ in the Iron-responsive Element of L-ferritin Causing Hereditary Hyperferritinaemia-cataract Syndrome.” Scientific Reports 7.
APA
Van De Sompele, S., Pécheux, L., Couso, J., Meunier, A., Sanchez, M., & De Baere, E. (2017). Functional characterization of a novel non-coding mutation “Ghent +49A>G” in the iron-responsive element of L-ferritin causing hereditary hyperferritinaemia-cataract syndrome. SCIENTIFIC REPORTS, 7.
Vancouver
1.
Van De Sompele S, Pécheux L, Couso J, Meunier A, Sanchez M, De Baere E. Functional characterization of a novel non-coding mutation “Ghent +49A>G” in the iron-responsive element of L-ferritin causing hereditary hyperferritinaemia-cataract syndrome. SCIENTIFIC REPORTS. 2017;7.
MLA
Van De Sompele, Stijn, Lucie Pécheux, Jorge Couso, et al. “Functional Characterization of a Novel Non-coding Mutation ‘Ghent +49A>G’ in the Iron-responsive Element of L-ferritin Causing Hereditary Hyperferritinaemia-cataract Syndrome.” SCIENTIFIC REPORTS 7 (2017): n. pag. Print.