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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
- Source :
- Scientific Reports, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, instname, Scientific reports, 7 (1, Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017), SCIENTIFIC REPORTS
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
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.<br />SCOPUS: ar.j<br />info:eu-repo/semantics/published
- Subjects :
- Male
0301 basic medicine
Proband
Untranslated region
lcsh:Medicine
PHENOTYPE
medicine.disease_cause
FAMILIES
0302 clinical medicine
BINDING
Medicine and Health Sciences
Hereditary hyperferritinemia-cataract syndrome
DNA sequencing
lcsh:Science
Child
Síndrome de hiperferritinemia-cataracta hereditaria
Síndrome d'hiperferritinèmia-cataracta hereditària
Mutation
LIGHT-CHAIN
Multidisciplinary
biology
Mutacions heterozigotes
Pedigree
Bilateral Cataracts
Heterozygous mutations
WEB SERVER
disease genetics
Female
MESSENGER-RNA
functional genomics
Mutations
Mutacions
Mutaciones heterocigotas
Adult
Adolescent
Iron
Consanguinity
Cataract
Article
genetic testing
03 medical and health sciences
consanguinity
Phénomènes atmosphériques
medicine
Humans
Gene
lcsh:R
Biology and Life Sciences
GENE
Iron Metabolism Disorders
Molecular biology
Zygosity
Ferritin
LENS
030104 developmental biology
Apoferritins
030221 ophthalmology & optometry
biology.protein
Mutaciones
lcsh:Q
MOLECULAR FINDINGS
Subjects
Details
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, instname, Scientific reports, 7 (1, Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017), SCIENTIFIC REPORTS
- Accession number :
- edsair.doi.dedup.....ff81ec219df7c1ba26f933f1e1495df5