Genetic and Clinical Characterization of Early-Onset High Myopia With or Without Cataract Due to Biallelic P3H2 Variants.

P3H2

Biallelic P3H2 variants (17 pathogenic or likely pathogenic variants, all previously unreported)

Using exome data from 17,045 unrelated probands with various eye conditions, this study searches for biallelic variants in P3H2, a known cause of autosomal recessive early-onset high myopia with or without cataract. Seventeen pathogenic or likely pathogenic variants, all previously unreported, were found in 11 patients from 11 of 1351 families with early-onset high myopia (0.81%) and in none of 15,694 families without it (P = 7.5 × 10⁻¹³). All patients had high myopia (mean spherical equivalent −12.29 diopters, mean age at diagnosis 3.55 years) and 4 of 11 had cataract, appearing as superior or temporal peripheral opacities visible only after full mydriasis; in a pooled analysis with published cases, cataract increased significantly with age. Longitudinal follow-up showed a paradoxical hyperopic shift despite continued axial elongation.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

P3H2 emerges as a relatively common cause of recessive early-onset high myopia, with a frequency comparable to LOXL3 and LRPAP1 according to the authors, and should therefore be routinely interpreted on a childhood high-myopia exome. The most useful message is ophthalmological: look for peripheral cataract after full mydriasis and monitor it with age, with the dissociation between refraction and axial length serving as a diagnostic clue. Eleven patients from a single population, with no functional study of the variants.

Analysis by Dr Thibaut Benquey