Τίτλος:
Hereditary hyperferritinemia cataract syndrome in three unrelated
families of western Greek origin caused by the C39 > G mutation of
L-ferritin IRE
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Hereditary hyperferritinemia-cataract syndrome (HHCS) is a
well-characterized autosomal dominant disease caused by mutations in the
iron responsive element (IRE) of ferritin L-chain (FTL) mRNA. Mutations
in the IRE result in reduced binding of the trans-acting iron regulatory
proteins (IRPs) and hence in upregulation of ferritin L-chain synthesis.
The disease is characterized by increased L-ferritin in serum and
tissues and early onset of bilateral cataracts. Iron metabolism is
normal, and there is no tissue iron overload. At least 25 nucleotide
substitutions and deletions in the L-ferritin IRE have been described in
families with HHCS, originating from diverse European, Australian and
North American populations. We studied the molecular pathogenesis of
HHCS in three unrelated kinderships of western Greek origin, with 19
affected members. We identified a relatively rare C39G mutation located
in the hexanucleotide loop of L-ferritin IRE. Computational analysis of
mRNA folding of mutant FTL IRE predicted that the C39 > G mutation leads
to a rearrangement of base pairing in this critical region, which is
likely to modify the IRP binding affinity. All subjects with HHCS were
heterozygotes for the same C39G mutation. Clinical and laboratory
phenotypes were described. Moreover, there was evidence of an
association between this FTL IRE stem-loop mutation and very high
ferritin levels. Our findings broaden the list of populations where HHCS
has been described. (c) 2005 Elsevier Inc. All rights reserved.
Συγγραφείς:
Papanikolaou, G
Chandrinou, H
Bouzas, E and
Contopoulos-Ioannidis, D
Kalotychou, V
Prentzas, K
Lilakos,
K
Asproudis, I
Palaiologou, D
Premetis, E
Papassotiriou,
I
Sakellaropoulos, N
Περιοδικό:
BLOOD CELLS MOLECULES AND DISEASES
Εκδότης:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Λέξεις-κλειδιά:
hyperferritinemia; cataract; Greece; IRE; iron; iron overload
DOI:
10.1016/j.bcmd.2005.10.003
