Hematologic biomarkers in childhood cataracts

Abstract

Purpose: To date, more than thirty nine genetic loci have been associated with congenital cataracts. Despite this progress, current diagnostic techniques are insufficient for unraveling the underlying genetic defect in sporadic patients and small families. In the present manuscript we demonstrate the contribution of routine laboratory tests in the search for genetic defects of childhood cataracts.

Methods: Two families with congenital cataracts and hematologic findings that included hyperferritinemia and the "ii" blood type underwent detailed ophthalmologic and clinical examinations. Mutation analysis of the ferritin light chain (FTL) and glucosaminyl (N-acetyl) transferase 2, I-branching enzyme (GCNT2) genes was performed in the two families, respectively.

Results: In the family with the "ii" blood group we found a novel GCNT2 mutation c.G935A (p.G312D) in the cataract patients, while in the family with hyperferritinemia cataract syndrome we identified a G→C heterozygous mutation at position +32 of FTL.

Conclusions: Hematologic biomarkers may simplify the search for the underlying molecular defect in families with congenital cataract.

Figure 1

Clinical features and genetic analysis. A: Ashkenazi Jewish family pedigree affected by Hereditary Hyperferritinemia Cataract Syndrome. B: Slit-lamp retroilluminative view of the lens discloses nuclear cataract with prominent Y sutures. C: DNA sequence analysis of the IRE (iron responsive element) part of FTL (ferritin light chain). A heterozygous G→C change in the 5`-untranslated region (5`-UTR) at position +32 from transcription start site (c. −168G→C), is indicated by black arrow. D: Persian Jewish family pedigree affected by congenital cataract (no photograph available) and phenotype ii. E: DNA sequence analysis showing a homozygous G → A transition (indicated by black arrow) at cDNA position 935, resulting in a change of Glycine to Aspartic acid (p.G312D) of all three isoforms of GCNT2.