Background: Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant Mendelian disorder characterized by early onset cataracts and elevated levels of serum ferritin in the absence of iron overload. Numerous mutations associated with the development of HHCS have been reported in the 5' non-coding region of the ferritin light chain (FTL) gene in family studies. We present an FTL mutation in an Australian family with 10 HHCS-affected members spanning three generations.
Materials and methods: Blood and saliva samples were collected from affected and unaffected family members and DNA was extracted using commercially available kits (Qiagen). The complete sequencing of the iron-responsive element (IRE) of the FTL gene was analyzed using bi-directional genomic sequencing.
Results: A heterozygous single nucleotide substitution (c.-167 C>T) was identified in the proband and five affected family members (logarithm of the odds score [Z] = 3.61, recombination distance [θ = 0]). All affected individuals had previously been found to have high ferritin levels and early onset cataracts.
Conclusion: This is the first Australian report of the c.-167 C>T mutation in a large family with multiple affected individuals. This finding raises the possibility that identification of HHCS mutations may be an effective means of disease detection and may aid in facilitating appropriate genetic counseling.
Keywords: Cataracts; iron metabolism; iron responsive element; serum ferritin.