PITX2 – Peters Anomaly

PITX2 encodes a paired-like homeodomain transcription factor essential for anterior segment development of the eye. Peters anomaly is characterized by central corneal opacity and iridocorneal adhesions, occasionally accompanied by nystagmus or strabismus, and represents a form of anterior segment dysgenesis with significant risk of vision loss. Genetic heterogeneity is well recognized in Peters anomaly, and although mutations in CYP1B1 and FOXC1 are more common, rare PITX2 variants have been reported.

In a sequencing panel of 23 unrelated patients with histologically confirmed Peters anomaly, one individual was found to carry a heterozygous missense variant c.350C>G (p.Pro117Arg) in PITX2 (PMID:33304895). This variant affects a conserved residue within the homeodomain and was absent from unaffected relatives and control databases. No additional segregation data or Peters anomaly–specific functional studies have been reported for PITX2 to date.

Overall, the evidence linking PITX2 to Peters anomaly remains limited, with only a single proband reported and no corroborating functional or segregation data. Routine clinical testing for PITX2 in Peters anomaly may be considered in undiagnosed cases, but additional studies are required to establish this association.

Key Take-home: A rare heterozygous PITX2 missense variant has been observed in one Peters anomaly patient, but current evidence is limited and further validation is needed for clinical application.

References

• Frontiers in cell and developmental biology • 2020 • Novel Mutations in COL6A3 That Associated With Peters' Anomaly Caused Abnormal Intracellular Protein Retention and Decreased Cellular Resistance to Oxidative Stress. PMID:33304895
• PITX2 | Peters anomaly

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