A clinico-genetic study of renal coloboma syndrome in children

Renal coloboma syndrome (RCS) is an autosomal dominant disorder caused by PAX2 gene mutations and characterized by renal hypoplasia and optic disc coloboma. The clinical findings were retrospectively reviewed, and all coding regions of the PAX2 gene were sequenced, in six children with RCS. A c.619_620insG mutation was detected in five patients, including two siblings, and a novel p.Arg104X mutation was detected in one patient. All the patients had progressive renal dysfunction and bilateral hypoplastic kidneys without vesicoureteral reflux (VUR), but the rate of progression to end-stage renal disease showed some diversity. The ocular manifestations showed wide variability, ranging from subtle optic disc anomalies to microphthalmia. In one family with two affected siblings, maternal germline mosaicism was suggested by an intragenic microsatellite marker study. In conclusion, there are variable renal and ocular manifestations in RCS without significant phenotype-genotype correlations. VUR is not a cardinal renal manifestation of RCS. The possibility of germline mosaicism should be considered during molecular diagnosis and genetic counseling for PAX2 mutations.