Discordant phenotype in monozygotic twins with renal coloboma syndrome and a PAX2 mutation.
BACKGROUND
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.


METHODS
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).


CONCLUSIONS
The patients described provide an extreme example of clinical variability in RCS. The role of environmental, genetic, and epigenetic factors is discussed.
Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Via G.B. Camozzi 3, 24020, Ranica (BG), Italy. paraskevas.iatropoulos@marionegri.it
Paraskevas
P
Iatropoulos
Erica
E
Daina
Caterina
C
Mele
Ramona
R
Maranta
Giuseppe
G
Remuzzi
Marina
M
Noris
D019943:Amino Acid Substitution; D002675:Child, Preschool; D003103:Coloboma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D003545:Cysteine; D018450:Disease Progression; D004200:Diseases in Twins / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D051762:PAX2 Transcription Factor / Q000235:genetics*; D010641:Phenotype; D051437:Renal Insufficiency / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D012307:Risk Factors; D014430:Twins, Monozygotic / Q000235:genetics*; D014718:Vesico-Ureteral Reflux / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D055815:Young Adult
D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D003545:Cysteine