Next-Generation Sequencing to Identify Genetic Causes of Chinese Patients Affected With Non-retinal Developmental Eye Disorders.

PAX6

Variants in 16 eye development genes (BMP4, BCOR, PITX3, PAX6…), including a splice-altering PAX6 intronic variant

This study analyses 14 Chinese families with non-retinal developmental eye disorders (microphthalmia, anterior segment dysgenesis including Peters anomaly, iris coloboma or aniridia, primary congenital glaucoma, congenital cataract, and one case of Rubinstein-Taybi syndrome), investigated by a targeted panel or exome sequencing, with Sanger segregation. Initial inheritance patterns were recessive in 1 family, dominant in 5 and sporadic in 8. Seventeen pathogenic or likely pathogenic variants and one variant of uncertain significance were identified in 16 genes, including BMP4, BCOR, PITX3 and PAX6; eight were novel and two de novo. The pathogenicity of a PAX6 intronic variant was confirmed by in vitro splicing assay, and the variant of uncertain significance was reclassified as likely pathogenic.

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

A small, heterogeneous series whose main interest lies in the functional demonstration of a PAX6 intronic variant by splicing assay, a reminder that such variants often escape routine interpretation. The diversity of 16 genes for 14 families argues for exome or genome sequencing in these eye malformations. Detailed genotype-phenotype correlations are missing from the abstract.

Analysis by Dr Thibaut Benquey