Discordant phenotype in monozygotic twins with renal coloboma syndrome and a PAX2 mutation
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Renal coloboma syndrome (RCS) is a highly variable syndrome characterized by renal and ocular abnormalities. It is associated in about 50 % of cases with mutations of PAX2, a gene encoding a transcription factor required during development.
The case study involves two monozygotic twin sisters with RCS showing highly discordant phenotypes. Twin 1 was antenatally diagnosed with multiple cysts in the right kidney. She had complicated vacuum-assisted delivery with acute renal failure. She developed proteinuria at age 4 years, followed by a progressive rise in serum creatinine requiring renal replacement therapy at age 22. No ocular abnormalities have been detected. Twin 2 experienced rapidly reversible acute renal failure without renal morphological abnormalities at birth. At age 2 years, complete visual acuity loss of the left eye secondary to an optic disc coloboma was diagnosed. No significant events occurred until the age of 20, when clinical proteinuria was detected. Proteinuria remission was obtained by multidrug treatment. In both patients, a novel de novo mutation of PAX2 was detected, which leads to the substitution of a highly conserved cysteine (p.C52Y).
The patients described provide an extreme example of clinical variability in RCS. The role of environmental, genetic, and epigenetic factors is discussed.
KeywordsRenal coloboma syndrome Papillorenal syndrome PAX2 Twins Phenotypic discordance Rare diseases
The authors wish to thank the patients and their parents for the availability to participate in the study. C.M. and R.M. are recipients of fellowships from Fondazione ART per la Ricerca sui Trapianti ONLUS (Milan, Italy) and from Fondazione Aiuti per la Ricerca sulle Malattie Rare (ARMR), Bergamo, Italy, respectively. The authors also wish to thank Mrs. Sara Gamba for her contribution in the management of the patients and Dr. Irene van der Meer for carefully reading and editing the manuscript.
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