Novel Genetic Variants and Clinical Profiles in Peters Anomaly Spectrum Disorders.

Peters anomaly (PA) is a rare congenital disorder within the anterior segment dysgenesis (ASD) spectrum, characterized by corneal opacity, iridocorneal adhesions, and potential systemic involvement. The genetic basis of PA and related syndromes are complex and incompletely understood. This study investigates novel genetic variants and their clinical impact in two unrelated individuals diagnosed with PA spectrum disorder. Whole-exome sequencing (WES), long-range PCR, and breakpoint analysis were applied to identify pathogenic variants. In the first patient, a heterozygous ~1.6 Mb deletion was detected, spanning the genes and (GRCh37 chr8:g.76760782_78342600del). The second patient carried a heterozygous variant (NM_001453.3:c.310A>G), classified as likely pathogenic. Both variants were confirmed by Sanger sequencing and considered de novo, as they were not present in the biological parents. Clinical evaluations revealed phenotypic variability, with the first patient displaying both ocular and systemic anomalies as in a Peters plus-like syndrome phenotype, while the second patient had isolated ocular manifestations as in a PA type 1 phenotype. These findings expand the genetic landscape of PA, underscoring the importance of comprehensive genomic analysis in subclassifying ASD disorders. Further studies are needed to elucidate the functional consequences of these variants and improve diagnostic and therapeutic strategies.