To present a novel Finnish double nucleotide variant in the iron-responsive element (IRE) of the ferritin L-chain gene (FTL) leading to hyperferritinaemia-cataract syndrome (HHCS).
Mutation profiling of positional-candidate genes detected a heterozygous, noncoding G-to-T transversion (c.-168G>T) located in the iron response element (IRE) of the gene coding for ferritin light chain (FTL) that cosegregated with cataract in the family.
Ferritin levels and age of cataract surgery varied among subjects with both FTL gene mutations, suggesting that phenotypic variability is modulated by other genetic or environmental factors.
Ferritin is of particular interest with regard to cataract because (i) cataract occurs in individuals with hereditary hyperferritinemia cataract syndrome (HHCS), a condition in which ferritin light chain (L-ferritin) protein is overexpressed systemically, and (ii) ferritin is an important regulator of oxidative stress, a primary factor in the etiology of aging-related cataract.
Mutations of the ferritin L-subunit gene in the iron-responsive element were identified, with autosomal dominant inherited cataract associated with hyperferritinemia.