Ferritin light chain gene mutations in two Brazilian families with hereditary hyperferritinemia-cataract syndrome

Abstract

Hereditary hyperferritinemia-cataract syndrome is an autosomal dominant genetic disorder associated with mutations in the 5’UTR region of the ferritin light chain gene. These mutations cause the ferritin levels to increase even in the absence of iron overload. Patients also develop bilateral cataract early due to accumulation of ferritin in the lens, and many are misdiagnosed as having hemochromatosis and thus not properly treated. The first cases were described in 1995 and several mutations have already been identified. However, this syndrome is still a poorly understood. We report two cases of unrelated Brazilian families with clinical suspicion of the syndrome, which were treated in our department. For the definitive diagnosis, the affected patients, their parents and siblings were submitted to Sanger sequencing of the 5’UTR region for detection of the ferritin light gene mutation. Single nucleotide polymorphism-like mutations were found in the affected patients, previously described. The test assisted in making the accurate diagnosis of the disease, and its description is important so that the test can be incorporated into clinical practice.

Genotypic–Phenotypic Correlations of Hereditary Hyperferritinemia-Cataract Syndrome: Case Series of Three Brazilian Families

“…Other previous cases of coinheritance of alleles in FTL and HFE have been described [9,18,19], but without comparing the relationship between HHCS phenotype in individuals with the same variants in FTL and HFE. It is important to note that heterozygosis in HFE is not uncommon in the Caucasian population, and about 25% of individuals are heterozygotic for c.187C>G (p.H63D).…”

“…Only five Brazilian families have previously been reported with HHCS [17][18][19]. The purpose of this case series is to describe three new Brazilian families with HHCS, as well as to discuss phenotype-genotype correlations.…”

Brazilian family with hyperferritinemia-cataract syndrome: case report

“…The 5'UTR region of the FTL and iron-regulating proteins are involved in the regulation of intracellular iron concentration. (5)(6)(7)(8)(9)(10) Rather than a single mutational origin, several mutations of the FTL gene can trigger HHCS.…”