Anterior Bipolar Cataract : A Novel Lens Phenotype Associated With CRYGD and L–Ferritin Mutations

Abstract

Abstract: : Purpose: To expand the phenotypic spectrum of aculeiform cataract (AC) and hereditary hyperferritinemia cataract syndrome (HHCS). Aculeiform cataract is caused by an R58H mutation in exon 2 of gamma–crystallin D (CRYGD) on chromosome 2q33–35. This autosomal dominant congenital and non progressive cataract is characterized by specific needle–like crystalloid lens opacifications. HHCS is an autosomal dominant condition featuring hyperferritinemia and cataract caused by point mutations in the iron–responsive element (IRE) of the L–Ferritin gene (FTL) on 19q13.3–q13.4. The lens phenotype is here slowly progressive and consists of characteristic cluster–like aggregates within the epinucleus, sparing the foetal nucleus and elongated vacuoles at the equator. Methods: 10 related HHCS and 29 AC patients belonging to 6 unrelated pedigrees were ascertained clinically and molecularly. Mutation analysis of the coding sequence of CRYGD and FTL genes was performed by bidirectional direct sequencing following PCR amplification. Each patient underwent a full lens phenotyping by slit–lamp and Scheimflug photography. Light and electronic microscopy was performed after surgery in selected cases. Results: In the aculeiform group, 56 eyes (26 bilateral and 2 unilateral cases) were examined and displayed the pathognomonic lens phenotype. However an anterior polar cataract was present in 9 eyes (16%) with a bipolar pattern in 4 of them. The R58H CRYGD mutation was found in all patients. In the HHCS family, the 20 eyes shared the typical cortical phenotype. However, in 4 eyes (20%), an anterior polar cataract was also documented, with a bipolar pattern in one eye. The disease phenotype cosegregated in all patients with a (+40A>G) mutation in the IRE of FTL. Light microscopy of the anterior capsule revealed degenerated anterior cortical fibers and collagen deposition. Electron microscopy showed dense crystalloid bodies. Conclusions: This study not only expands the clinical phenotype spectrum of CRYGD and FTL mutations, but is also the first to identify genetic defects causing anterior polar cataract and to describe the bipolar variant of these well defined clinical entities.

Keywords: cataract • genetics