A new mutation (G51C) in the iron-responsive element (IRE) of L-ferritin associated with hyperferritinaemia-cataract syndrome decreases the binding affinity of the mutated IRE for iron-regulatory proteins

Clara Camaschella, G. Zecchina, G. Lockitch, A. Roetto, A. Campanella, P. Arosio, S. Levi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Hereditary hyperferritinaemia-cataract syndrome is an autosomal dominant disorder characterized by a constitutively increased synthesis of L-ferritin in the absence of iron overload. The disorder is associated with point mutations in the iron-responsive element (IRE) of L-ferritin mRNA. We report a new mutation, G51C, identified in two members of a Canadian family, presenting a moderate increase in serum ferritin and a clinically silent bilateral cataract. Gel retardation assays showed that the binding of the mutated IRE to iron-regulatory proteins (IRPs) was reduced compared with the wild type. Structural modelling predicted that the G51C induces a rearrangement of base pairing at the lateral bulge of the IRE structure which is likely to modify IRE conformation.

Original languageEnglish
Pages (from-to)480-482
Number of pages3
JournalBritish Journal of Haematology
Volume108
Issue number3
DOIs
Publication statusPublished - 2000

Fingerprint

Iron-Regulatory Proteins
Apoferritins
Iron
Mutation
Iron Overload
Electrophoretic Mobility Shift Assay
Ferritins
Point Mutation
Base Pairing
Cataract
Messenger RNA
Hyperferritinemia, hereditary, with congenital cataracts
Serum

Keywords

  • Cataract
  • Ferritin
  • Iron-regulatory proteins
  • Iron-responsive element
  • Mutations

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "A new mutation (G51C) in the iron-responsive element (IRE) of L-ferritin associated with hyperferritinaemia-cataract syndrome decreases the binding affinity of the mutated IRE for iron-regulatory proteins",
abstract = "Hereditary hyperferritinaemia-cataract syndrome is an autosomal dominant disorder characterized by a constitutively increased synthesis of L-ferritin in the absence of iron overload. The disorder is associated with point mutations in the iron-responsive element (IRE) of L-ferritin mRNA. We report a new mutation, G51C, identified in two members of a Canadian family, presenting a moderate increase in serum ferritin and a clinically silent bilateral cataract. Gel retardation assays showed that the binding of the mutated IRE to iron-regulatory proteins (IRPs) was reduced compared with the wild type. Structural modelling predicted that the G51C induces a rearrangement of base pairing at the lateral bulge of the IRE structure which is likely to modify IRE conformation.",
keywords = "Cataract, Ferritin, Iron-regulatory proteins, Iron-responsive element, Mutations",
author = "Clara Camaschella and G. Zecchina and G. Lockitch and A. Roetto and A. Campanella and P. Arosio and S. Levi",
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T1 - A new mutation (G51C) in the iron-responsive element (IRE) of L-ferritin associated with hyperferritinaemia-cataract syndrome decreases the binding affinity of the mutated IRE for iron-regulatory proteins

AU - Camaschella, Clara

AU - Zecchina, G.

AU - Lockitch, G.

AU - Roetto, A.

AU - Campanella, A.

AU - Arosio, P.

AU - Levi, S.

PY - 2000

Y1 - 2000

N2 - Hereditary hyperferritinaemia-cataract syndrome is an autosomal dominant disorder characterized by a constitutively increased synthesis of L-ferritin in the absence of iron overload. The disorder is associated with point mutations in the iron-responsive element (IRE) of L-ferritin mRNA. We report a new mutation, G51C, identified in two members of a Canadian family, presenting a moderate increase in serum ferritin and a clinically silent bilateral cataract. Gel retardation assays showed that the binding of the mutated IRE to iron-regulatory proteins (IRPs) was reduced compared with the wild type. Structural modelling predicted that the G51C induces a rearrangement of base pairing at the lateral bulge of the IRE structure which is likely to modify IRE conformation.

AB - Hereditary hyperferritinaemia-cataract syndrome is an autosomal dominant disorder characterized by a constitutively increased synthesis of L-ferritin in the absence of iron overload. The disorder is associated with point mutations in the iron-responsive element (IRE) of L-ferritin mRNA. We report a new mutation, G51C, identified in two members of a Canadian family, presenting a moderate increase in serum ferritin and a clinically silent bilateral cataract. Gel retardation assays showed that the binding of the mutated IRE to iron-regulatory proteins (IRPs) was reduced compared with the wild type. Structural modelling predicted that the G51C induces a rearrangement of base pairing at the lateral bulge of the IRE structure which is likely to modify IRE conformation.

KW - Cataract

KW - Ferritin

KW - Iron-regulatory proteins

KW - Iron-responsive element

KW - Mutations

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