TY - JOUR
T1 - Discordant phenotype in monozygotic twins with renal coloboma syndrome and a PAX2 mutation
AU - Iatropoulos, Paraskevas
AU - Daina, Erica
AU - Mele, Caterina
AU - Maranta, Ramona
AU - Remuzzi, Giuseppe
AU - Noris, Marina
PY - 2012/10
Y1 - 2012/10
N2 - 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. Case-Diagnosis/Treatment: 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.
AB - 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. Case-Diagnosis/Treatment: 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.
KW - Papillorenal syndrome
KW - PAX2
KW - Phenotypic discordance
KW - Rare diseases
KW - Renal coloboma syndrome
KW - Twins
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U2 - 10.1007/s00467-012-2205-x
DO - 10.1007/s00467-012-2205-x
M3 - Article
C2 - 22660956
AN - SCOPUS:84867002295
VL - 27
SP - 1989
EP - 1993
JO - Pediatric Nephrology
JF - Pediatric Nephrology
SN - 0931-041X
IS - 10
ER -