PAX6 – Aniridia-Cerebellar Ataxia-Intellectual Disability Syndrome

A single sporadic patient presenting with partial aniridia, foveal hypoplasia, and cerebellar hypoplasia was found to carry a de novo intronic PAX6 variant, c.-129+2T>A (PMID:17148041), with no family history and no affected relatives. However, in three unrelated families (two autosomal recessive pedigrees totaling six affected individuals) and in 11 additional Gillespie syndrome cases, no PAX6 mutations or linkage to the PAX6 locus were detected (PMID:8188215; PMID:27124303). This pattern, combined with the absence of segregation data, supports a disputed role for PAX6 in this syndrome.

No functional assays have demonstrated PAX6 involvement in the cerebellar or cognitive components of Gillespie syndrome, and existing PAX6 functional studies pertain exclusively to classic aniridia phenotypes. Given the preponderance of negative genetic screens and lack of mechanistic evidence, routine PAX6 testing is not supported for patients with aniridia-cerebellar ataxia-intellectual disability syndrome.

References

• American journal of ophthalmology • 1998 • Gillespie syndrome phenotype with a t(X;11)(p22.32;p12) de novo translocation. PMID:9512164
• Genomics • 1994 • Absence of PAX6 gene mutations in Gillespie syndrome (partial aniridia, cerebellar ataxia, and mental retardation). PMID:8188215
• PloS one • 2016 • Genetic Analysis of 'PAX6-Negative' Individuals with Aniridia or Gillespie Syndrome. PMID:27124303
• Ophthalmic genetics • 2006 • Ocular findings in Gillespie-like syndrome: association with a new PAX6 mutation. PMID:17148041

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