ORIGINAL ARTICLE A clinico-genetic study of renal coloboma syndrome in children Hae Il Cheong & Hee Yeon Cho & Jeong Hun Kim & Young Suk Yu & Il Soo Ha & Yong Choi Received: 21 March 2007 / Revised: 29 April 2007 / Accepted: 8 May 2007 / Published online: 31 May 2007 # IPNA 2007 Abstract Renal coloboma syndrome (RCS) is an autoso- mal 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. Keywords Renal coloboma syndrome . PAX2 gene . Vesicoureteral reflux . Germline mosaicism Introduction Renal coloboma syndrome (RCS, OMIM #120330) is a rare, autosomal, dominant disorder caused by loss-of-function mutations in the PAX2 gene, which encodes a transcription factor. RCS is clinically characterized by renal malforma- tion (renal hypoplasia with variable degree of renal insufficiency) and optic disc coloboma. However, it is well known that PAX2 gene mutations are associated with both inter- and intra-familial phenotypic variability [1], and patients may have additional congenital anomalies, such as vesicoureteral reflux (VUR), loss of high-frequency hearing, central nervous system anomalies, and others (reviewed in [2]). This pattern of organ involvement is consistent with the pattern of PAX2 expression, i.e., in the developing eye, ear, kidney, ureteric bud, and midbrain/ hindbrain [3, 4]. In this study the phenotype and genotype of six children with RCS were analyzed and compared with those of previously reported cases. We found a novel PAX2 mutation, R104X, in one patient, and a common mutation, c.619_620insG, in five patients. The renal and ocular phenotypes were variable among the patients. None of the patients had VUR. In addition, maternal germline mosai- cism for the c.619_620insG mutation was suspected in one family. Pediatr Nephrol (2007) 22:1283–1289 DOI 10.1007/s00467-007-0525-z H. I. Cheong (*) : I. S. Ha : Y. Choi Department of Pediatrics, Seoul National University Children’ s Hospital, 28 Yongon-Dong, Chongro-Gu, Seoul 110-744, South Korea e-mail: cheonghi@snu.ac.kr H. Y. Cho Department of Pediatrics, Gachon University of Medicine and Science, Gil Medical Center, Incheon, South Korea J. H. Kim : Y. S. Yu Department of Ophthalmology, Seoul National University College of Medicine & Seoul Artificial Eye Center, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea