Introduction: Reports from around the world confirm that heterozygous PAX6 mutation is the major cause of hereditary aniridia (with a classic phenotype of iris hypoplasia, keratopathy, lens opacity, and foveal hypoplasia). However, genotype/phenotype reports are lacking from the Arabian Peninsula, a historically isolated region with a relatively high incidence of recessive disease and thus a potential for phenocopy and pseudodominance. The purpose of this study to assess for PAX6 mutation in two unrelated families with classic hereditary aniridia from the Arabian Peninsula.
Methods: Interventional cases series of two unrelated affected Saudi Arabian families. Available family members underwent ophthalmic examination and venous blood sampling for PAX6 sequencing.
Results: The pedigrees of both families suggested dominant (or pseudodominant) inheritance of the classic aniridia phenotype. Affected individuals in Family #1 were heterozygous for a novel frameshift PAX6 mutation (c.delA1294). Affected individuals in Family #2 had heterozygosity for a commonly-reported PAX6 nonsense mutation (p.Arg240X).
Conclusions: PAX6 haploinsufficiency, the major cause of classic hereditary aniridia worldwide, is also associated with the phenotype in two different families from the Arabian Peninsula. Homozygosity by descent is not expected to affect genotype/phenotype correlation for the classic phenotype.