PITX2 – Aniridia

Multiple large cohorts totaling 150 unrelated probands with aniridia have undergone PITX2 sequencing, but no pathogenic variants were identified. In a French series of 33 probands (27 congenital cataract, 6 aniridia) screening of FOXE3, PAX6, PITX2 and PITX3 revealed no PITX2 mutations ([PMID:20806047]). Similarly, 58 PAX6‐negative aniridia cases were negative for PITX2 coding variants ([PMID:23213277]), and analysis of 42 PAX6‐negative individuals (31 aniridia, 11 Gillespie syndrome) revealed no intragenic PITX2 changes ([PMID:27124303]). In a Cypriot cohort of 17 individuals from six families, sequencing of PAX6, FOXC1 and PITX2 detected PAX6 mutations in five families but none in PITX2 ([PMID:29901133]). No segregation or recurrent variants in PITX2 have been reported in aniridia.

Although PITX2 is essential for anterior segment development and its dysfunction underlies Axenfeld–Rieger syndrome, there is no functional or experimental evidence implicating PITX2 perturbation in isolated aniridia. The absence of PITX2 mutations across multiple well‐powered aniridia cohorts refutes a causative role. Key take-home: PITX2 sequencing is not indicated in the genetic workup of isolated aniridia.

References

• Molecular vision • 2010 • Identification of dominant FOXE3 and PAX6 mutations in patients with congenital cataract and aniridia. PMID:20806047
• Molecular vision • 2012 • Absence of NR2E1 mutations in patients with aniridia. PMID:23213277
• PloS one • 2016 • Genetic Analysis of 'PAX6-Negative' Individuals with Aniridia or Gillespie Syndrome. PMID:27124303
• Molecular medicine reports • 2018 • Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation. PMID:29901133

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