Bilateral juvenile-onset cataracts associated with GCNT2 variants

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Congenital cataracts are often linked to genetic factors.
• Mutations in the GCNT2 gene are associated with congenital cataracts.
• The GCNT2B isoform is specifically expressed in lens epithelial cells.

Purpose of the Study:

• To investigate the genetic basis of juvenile-onset cataracts in a pediatric patient.
• To identify novel variants in the GCNT2 gene associated with early-onset cataracts.
• To explore the role of the GCNT2B isoform in cataractogenesis.

Main Methods:

• Retrospective chart review of ophthalmic examinations.
• Next-generation sequencing (NGS) of 66 genes associated with early-onset cataracts.
• Analysis of GCNT2 gene variants, including a novel change in the GCNT2B isoform.

Main Results:

• An 8-year-old female presented with bilateral juvenile-onset cataracts diagnosed at age 6.
• Genetic testing revealed two GCNT2 variants: a pathogenic variant in exon 3 (c.1040A>G;p.Tyr347Cys) and a variant of uncertain significance in exon 1B (c.677G>T;p.Arg226Leu).
• The variant in exon 1B represents a novel missense change in the lens-specific GCNT2B transcript.

Conclusions:

• GCNT2 variants can cause cataracts presenting in childhood, not exclusively at birth.
• This study reports the first missense variant in the GCNT2B isoform, expanding the mutational spectrum for GCNT2-related cataracts.
• The findings suggest GCNT2B variants may contribute to juvenile-onset cataracts.