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K. Burdon, C. Chen, M. Delatycki, D. Dimasi, J. Craig; Hereditary Hyperferritinemia Cataract Syndrome In The Absence Of Ferritin Light Chain Mutations . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4620.
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Hereditary hyperferritinaemia cataract syndrome (HHCS) is characterized by a distinctive cataract morphology and high serum ferritin in the absence of iron overload. It is known to be caused by mutations in the iron regulatory element (IRE) of the Ferritin Light Chain (FTL) gene on chromosome 19q13.3. Here, we investigate the genetics of HHCS in two Australian kindreds with classical features of the disorder.
The index cases were identified by clinical lens photography showing classic HHCS cataract features and confirmed by serum ferritin measures. Family members were approached for medical history, lens photography and venepuncture for DNA extraction and iron studies including ferritin, total iron, transferrin and transferrin saturation. Genetic linkage to the FTL gene was assessed through the genotyping of three microsatellite markers in the region (GDB:636543, GDB:201826 and D19S879). Direct sequencing of the IRE as well as the remainder of the FTL gene were performed on an ABI PRISM 3100 instrument.
Family 1 is a three generation kindred with typical HHCS lens morphology and confirmed with haematological abnormalities of high ferritin levels in the absence of iron overload. Several additional family members were unavailable for study, but were also reported to have cataracts. This family was found to be consistent with linkage to the FTL gene, although no mutations in the gene itself were identified. Family 2 was investigated for isolated hyperferritinaemia and subsequently found to have HHCS. Additional family members were not available for linkage analysis. As with family 1, no mutations were found in the FTL gene.
While there are many reports of IRE mutations in HHCS patients in the literature, HHCS is not caused by mutations in the IRE of the FTL gene in these two families, nor is it contributed to by other mutations in the coding regions of this gene. This is the first report of HHCS with typical lens morphology and haematological features in the absence of an FTL mutation. These observations suggest other as yet undefined regulatory regions may contribute to ferritin dysregulation and in turn HHCS.
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