Denaturing gradient gel electrophoresis screening for mutations in the hereditary hyperferritinaemia cataract syndrome

Giansily, Muriel; Beaumont, Carole; Desveaux, C.; Hetet, Gilles; Schved, Jean‐François; Aguilar-Martinez, Patricia

doi:10.1046/j.1365-2141.2001.02513.x

Cited by 18 publications

(12 citation statements)

References 13 publications

(14 reference statements)

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“…6,14,16,21,22,26,27 Mutagenesis studies of (mRNA)FTL IREs in vitro suggest that the primary nucleotide sequence in the apical loop of the motif is an important determinant of IRP binding. 15,28 Our findings support this hypothesis since two of the observed nucleotide substitutions lay within the apical loop of the IRE motif.…”

Section: Discussionmentioning

confidence: 99%

“…12 Individuals with HHCS show point mutations or short deletions in the region of the FTL 5 0 UTR corresponding to the (mRNA)FTL IRE. 13,14 Nucleotide substitutions that disrupt the secondary structure of IRE stem-loop motifs reduce the affinity of IRP binding in vitro. 15 It has therefore been proposed that HHCS arises through disruption of the L-ferritin RP-IRE interaction in vivo leading to failure of suppression of constitutive translation of (mRNA)FTL.…”

Section: Introductionmentioning

confidence: 99%

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Clinical features and molecular analysis of seven British kindreds with hereditary hyperferritinaemia cataract syndrome

Lachlan¹,

Temple²,

Mumford

2004

Eur J Hum Genet

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Hereditary hyperferritinaemia cataract syndrome (HHCS) is an autosomal dominant disorder characterised by early onset cataracts and increased serum L-ferritin concentration. Affected individuals show nucleotide substitutions in the region of the L-ferritin gene (FTL) that encodes a regulatory sequence within the (mRNA)FTL termed the iron responsive element (IRE). We report the clinical features of seven HHCS kindreds containing 49 individuals with premature cataract. All the probands received diagnoses of HHCS after the incidental discovery of increased serum L-ferritin concentration (median 1420 lg/l; normal range 15 -360 lg/l), in most cases during investigation or screening for anaemia. All the probands developed characteristic 'sunflower' morphology cataracts in childhood (median age at diagnosis 5 years), but had no other phenotypic features. All the affected kindreds showed nucleotide substitutions in FTL that were predicted to disrupt function of the (mRNA)FTL IRE. The severity of the clinical phenotype of HHCS was variable both within and between kindreds and showed no clear relationship to FTL genotype. HHCS should be included in the differential diagnosis of hyperferritinaemia and should be carefully distinguished from hereditary haemochromatosis. Measurement of the serum L-ferritin concentration should be included in the investigation of all individuals with early onset cataracts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical features and molecular analysis of seven British kindreds with hereditary hyperferritinaemia cataract syndrome

Lachlan¹,

Temple²,

Mumford

2004

Eur J Hum Genet

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“…Slit-lamp examination, direct illumination and retro-illumination of his lenses showed scattered, radially oriented flecks and crystalline deposits in both lenses (Figure 2). Sequencing of the FTL gene using a previously described method [6] showed a heterozygous c.33 C > A transversion in the IRE within the FTL 5'UTR. This mutation has been previously associated with the HHCS phenotype [6].…”

Section: Case Presentationsmentioning

confidence: 99%

“…Sequencing of the FTL gene using a previously described method [6] showed a heterozygous c.33 C > A transversion in the IRE within the FTL 5'UTR. This mutation has been previously associated with the HHCS phenotype [6]. …”

Section: Case Presentationsmentioning

confidence: 99%

Hyperferritinemia without iron overload in patients with bilateral cataracts: a case series

et al. 2011

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IntroductionHepatologists and internists often encounter patients with unexplained high serum ferritin concentration. After exclusion of hereditary hemochromatosis and hemosiderosis, rare disorders like hereditary hyperferritinemia cataract syndrome should be considered in the differential diagnosis. This autosomal dominant syndrome, that typically presents with juvenile bilateral cataracts, was first described in 1995 and has an increasing number of recognized molecular defects within a regulatory region of the L-ferritin gene (FTL).Case presentationTwo patients (32 and 49-year-old Caucasian men) from our ambulatory clinic were suspected as having this syndrome and a genetic analysis was performed. In both patients, sequencing of the FTL 5' region showed previously described mutations within the iron responsive element (FTL c.33 C > A and FTL c.32G > C).ConclusionHereditary hyperferritinemia cataract syndrome should be considered in all patients with unexplained hyperferritinemia without signs of iron overload, particularly those with juvenile bilateral cataracts. Liver biopsy and phlebotomy should be avoided in this disorder.

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“…Most of the IRE mutations responsible for HHCS are point mutations and only three deletions have been reported so far (Cremonesi et al, 2001;Giansily et al, 2001). In this paper we describe a novel six-base deletion identified in an Italian family presenting with elevated serum ferritin and severe bilateral cataract.…”

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confidence: 91%

A novel deletion of the l‐ferritin iron‐responsive element responsible for severe hereditary hyperferritinaemia–cataract syndrome

et al. 2002

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Summary. In the last few years, mutations that cause disease through increased efficiency of mRNA translation have been discovered. Hereditary hyperferritinaemia-cataract syndrome (HHCS) arises from various point mutations or deletions within the iron-responsive element (IRE) in the 5¢-UTR of the l-ferritin mRNA. Each unique mutation confers a characteristic degree of hyperferritinaemia and severity of cataract in affected individuals. We report a novel six-nucleotide deletion identified in an Italian family presenting with elevated serum ferritin and early onset bilateral cataract. This deletion involves a sequence with a TCT repetition and may have occurred through a mechanism of slippage mispairing. Because of the above repetition, the observed mutation can be interpreted as deletion 22-27, 23-28, 24-29 or 25-30. Structural modelling predicted an IRE stem modification that is expected to markedly reduce the binding to iron-regulatory proteins. A double-gradient denaturing gradient gel electrophoresis (DG-DGGE) method easily detected the above deletion.

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Denaturing gradient gel electrophoresis screening for mutations in the hereditary hyperferritinaemia cataract syndrome

Cited by 18 publications

References 13 publications

Clinical features and molecular analysis of seven British kindreds with hereditary hyperferritinaemia cataract syndrome

Clinical features and molecular analysis of seven British kindreds with hereditary hyperferritinaemia cataract syndrome

Hyperferritinemia without iron overload in patients with bilateral cataracts: a case series

A novel deletion of the l‐ferritin iron‐responsive element responsible for severe hereditary hyperferritinaemia–cataract syndrome

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