Early Onset Cataracts

Study provides insights on genetic pathways in early-onset bilateral cataracts

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A new observational study has shed light on the genetic factors contributing to acquired early-onset bilateral cataracts, which can arise from systemic etiologies or genetic disorders.

Researchers conducted next-generation sequencing on 347 individuals, aged 18 months to 35 years, to identify disease-causing genetic variants.

The study found that most patients (90.2%) were under 19 years old, with a median age of 8 years. Of the 347 participants, 69 patients (19.9%) exhibited 74 pathogenic or likely pathogenic genetic variants. These included 64 single nucleotide variants across 24 genes and 10 copy number variants (CNVs) of varying sizes and genomic locations.

Key findings include:

  • Crystallin genes were a common source of mutations, representing 27.0% of all identified variants.
  • Notable recurrent variants included:
    • CRYBA1 c.215+1G>A, found in 3 patients.
    • CRYBA1 c.272_274delGAG, CRYBB2 c.463C>T, c.562C>T, and CRYAA c.62G>A, each observed in 2 patients.
  • CNV deletions associated with 1q21.1 microdeletion syndrome were detected in 5 patients.

A particularly significant finding was the identification of biallelic variants in CYP27A1 in 2 siblings, leading to a diagnosis of cerebrotendinous xanthomatosis—a rare but treatable condition often presenting with early-onset bilateral cataracts.

This research highlights the potential of genetic insights to improve diagnostic accuracy and treatment outcomes for individuals affected by early-onset bilateral cataracts.

Fox JC, Dutta R, Nihalani BR, Ponte A, et al. Identification of pathogenic genetic variants in patients with acquired early-onset bilateral cataracts using next-generation sequencing. J AAPOS. 2024;28(1):103808. doi: 10.1016/j.jaapos.2023.11.011. Epub 2024 Jan 10. PMID: 38216115.