Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330) |
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Authors: | K. Devriendt Gert Matthijs Boudewijn Van Damme Daniel Van Caesbroeck Michael Eccles Yves Vanrenterghem Jean-Pierre Fryns Anita Leys |
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Affiliation: | (1) Center for Human Genetics, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium e-mail: koen.devriendt@med.kuleuven.ac.be, Tel.: +32-16-34-58-99, Fax: +32-16-34-60-51, BE;(2) Department of Pathology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium, BE;(3) Algemeen Ziekenhuis St Jozef, Nephrology Unit, Turnhout, Belgium, BE;(4) University of Otago, Dept. of Biochemistry, Dunedin, New Zealand, NZ;(5) Department of Nephrology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium, BE;(6) Department of Ophthalmology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium, BE |
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Abstract: | We present a family with autosomal-dominant inheritance of renal insufficiency caused by renal hypoplasia in six individuals. In all affected individuals, signs of optic disk dysplasia were detected, but most patients were asymptomatic. A heterozygous missense mutation in the PAX2 gene causing a Gly75 to Ser substitution was present in all affected individuals. A second, unrelated patient presented with ocular complaints related to optic disk dysplasia, and had a history of vesico-ureteral reflux. A heterozygous hexanucleotide duplication in the PAX2 gene was detected leading to the duplication of GluThr at positions 74 and 75. The mutations in these two families are the first mutations in the PAX2 gene that do not lead to a truncated protein. Mechanistically, these mutations are expected to result in abnormal folding of the PAX2 protein. These observations further expand the spectrum of clinical features associated with PAX2 mutations, and suggest that a distinct genetic disorder can be identified in patients with renal dysplasia through a careful eye examination. As the ocular manifestations in this syndrome are variable anomalies of retinal and optic disk dysplasia, we prefer the term “papillo-renal syndrome”. Received: 29 January 1998 / Accepted: 25 March 1998 |
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