FURTHER DELINEATION OF RENAL-COLOBOMA SYNDROME IN PATIENTS WITH EXTREME VARIABILITY OF PHENOTYPE AND IDENTICAL PAX2 MUTATIONS

Renal-coloboma syndrome is a recently described autosomal dominant syn drome of abnormal optic nerve and renal development. Two families have been reported with renal-coloboma syndrome and mutations of the PAX2 gene, The PAX2 gene, which encodes a DNA-binding protein, is expressed in the developing ear, CNS, eye, and urogenital tract. Ocular and/or renal abnormalities have been consistently noted in the five reports o f patients with renal-coloboma syndrome, to date, but PAX2 expression patterns suggest that auditory and CNS abnormalities may be additional features of renal-coloboma syndrome. To determine whether additional clinical features are associated with PAX2 mutations, we have used PCR -SSCP to identify PAX2 gene mutations in patients. We report here four patients with mutations in exon 2, one of whom has severe ocular and renal disease, microcephaly, and retardation, and another who has ocul ar and renal disease with high-frequency hearing loss; Unexpectedly, e xtreme variability in clinical presentation was observed between a mot her, her son, and an unrelated patient, all of whom had the same PAX2 mutation as previously described in two siblings with renal-coloboma s yndrome. These results suggest that a sequence of seven Gs in PAX2 exo n 2 may be particularly prone to mutation.