Abstract
Hereditary hyperferritinaemia-cataract syndrome (HHCS) is an autosomal dominant disease caused by mutations in the iron responsive element (IRE) of the L-ferritin gene. Despite the elucidation of the genetic basis, the overall clinical spectrum of HHCS has been less well studied as, to date, only individual case reports have been described. Therefore, we studied a total of 62 patients in 14 unrelated families, with nine different mutations. No relevant symptoms other than visual impairment were found to be associated with the syndrome. A marked phenotypic variability was observed, particularly with regard to ocular involvement (i.e. age range at which cataract was diagnosed in 16 subjects with the C39T: 6-40 years). Similarly, serum ferritin levels varied substantially also within subjects sharing the same mutation (i.e. range for the A40G: 700- 2412 μg/l). We followed an HHCS newborn in whom well-defined lens opacities were not detectable either at birth or at 1 year. The lens ferritin content was analysed in two subjects who underwent cataract surgery at different ages, with different cataract morphology. Values were similar and about 1500-fold higher than in controls. These observations suggest that: (i) in HHCS the cataract is not necessarily congenital; (ii) in addition to the IRE genotype, other genetic or environmental factors may modulate the phenotype, especially the severity of the cataract.
| Original language | English |
|---|---|
| Pages (from-to) | 334-340 |
| Number of pages | 7 |
| Journal | British Journal of Haematology |
| Volume | 115 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2001 |
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Keywords
- Cataract
- Ferritin
- Hyperferritinaemia-cataract syndrome
- Iron responsive element
- Lens
ASJC Scopus subject areas
- Hematology
Cite this
Clinical, biochemical and molecular findings in a series of families with hereditary hyperferritinaemia-cataract syndrome. / Girelli, Domenico; Bozzini, Claudia; Zecchina, Gabriella; Tinazzi, Elisa; Bosio, Sandra; Piperno, Alberto; Ramenghi, Ugo; Peters, Jutta; Levi, Sonia; Camaschella, Clara; Corrocher, Roberto.
In: British Journal of Haematology, Vol. 115, No. 2, 2001, p. 334-340.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical, biochemical and molecular findings in a series of families with hereditary hyperferritinaemia-cataract syndrome
AU - Girelli, Domenico
AU - Bozzini, Claudia
AU - Zecchina, Gabriella
AU - Tinazzi, Elisa
AU - Bosio, Sandra
AU - Piperno, Alberto
AU - Ramenghi, Ugo
AU - Peters, Jutta
AU - Levi, Sonia
AU - Camaschella, Clara
AU - Corrocher, Roberto
PY - 2001
Y1 - 2001
N2 - Hereditary hyperferritinaemia-cataract syndrome (HHCS) is an autosomal dominant disease caused by mutations in the iron responsive element (IRE) of the L-ferritin gene. Despite the elucidation of the genetic basis, the overall clinical spectrum of HHCS has been less well studied as, to date, only individual case reports have been described. Therefore, we studied a total of 62 patients in 14 unrelated families, with nine different mutations. No relevant symptoms other than visual impairment were found to be associated with the syndrome. A marked phenotypic variability was observed, particularly with regard to ocular involvement (i.e. age range at which cataract was diagnosed in 16 subjects with the C39T: 6-40 years). Similarly, serum ferritin levels varied substantially also within subjects sharing the same mutation (i.e. range for the A40G: 700- 2412 μg/l). We followed an HHCS newborn in whom well-defined lens opacities were not detectable either at birth or at 1 year. The lens ferritin content was analysed in two subjects who underwent cataract surgery at different ages, with different cataract morphology. Values were similar and about 1500-fold higher than in controls. These observations suggest that: (i) in HHCS the cataract is not necessarily congenital; (ii) in addition to the IRE genotype, other genetic or environmental factors may modulate the phenotype, especially the severity of the cataract.
AB - Hereditary hyperferritinaemia-cataract syndrome (HHCS) is an autosomal dominant disease caused by mutations in the iron responsive element (IRE) of the L-ferritin gene. Despite the elucidation of the genetic basis, the overall clinical spectrum of HHCS has been less well studied as, to date, only individual case reports have been described. Therefore, we studied a total of 62 patients in 14 unrelated families, with nine different mutations. No relevant symptoms other than visual impairment were found to be associated with the syndrome. A marked phenotypic variability was observed, particularly with regard to ocular involvement (i.e. age range at which cataract was diagnosed in 16 subjects with the C39T: 6-40 years). Similarly, serum ferritin levels varied substantially also within subjects sharing the same mutation (i.e. range for the A40G: 700- 2412 μg/l). We followed an HHCS newborn in whom well-defined lens opacities were not detectable either at birth or at 1 year. The lens ferritin content was analysed in two subjects who underwent cataract surgery at different ages, with different cataract morphology. Values were similar and about 1500-fold higher than in controls. These observations suggest that: (i) in HHCS the cataract is not necessarily congenital; (ii) in addition to the IRE genotype, other genetic or environmental factors may modulate the phenotype, especially the severity of the cataract.
KW - Cataract
KW - Ferritin
KW - Hyperferritinaemia-cataract syndrome
KW - Iron responsive element
KW - Lens
UR - http://www.scopus.com/inward/record.url?scp=0035725363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035725363&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2141.2001.03116.x
DO - 10.1046/j.1365-2141.2001.03116.x
M3 - Article
C2 - 11703332
AN - SCOPUS:0035725363
VL - 115
SP - 334
EP - 340
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 2
ER -