TY - JOUR
T1 - WT1 Deletion Leading to Severe 46,XY Gonadal Dysgenesis, Wilms Tumor and Gonadoblastoma: Case Report
AU - Finken, Martijn J. J.
AU - Hendriks, Yvonne M. C.
AU - van der Voorn, J. Patrick
AU - Veening, Margreet A.
AU - Lombardi, M. Paola
AU - Rotteveel, Joost
PY - 2015
Y1 - 2015
N2 - Heterozygous missense mutations in the WT1 gene that affect the function of the wild-type allele have been identified in Denys-Drash syndrome, which is characterized by severe gonadal dysgenesis, early-onset nephropathy and a predisposition to renal and gonadal cancer. Intron 9 splice-site mutations that influence the balance between WT1 isoforms cause a nearly similar phenotype, known as Frasier syndrome. Nonsense mutations and deletions only lead to WT1 haploinsufficiency and, hence, to less severe gonadal dysgenesis and late-onset nephropathy. WT1 analysis is mandatory in 46,XY gonadal dysgenesis with renal abnormality. We describe a newborn with 46,XY severe partial gonadal dysgenesis, in whom structural renal anomalies and proteinuria were excluded. Gonadectomy was performed at the age of 1 month and the microscopy was thought to be suggestive for a gonadoblastoma. At the age of 9 months, the patient presented with a bilateral Wilms tumor. We found a heterozygous WT1 whole-gene deletion but no other gene defects. This case description illustrates that a WT1 deletion might be associated with a more severe phenotype than previously thought. It also illustrates that, even in the absence of renal abnormality, it is recommended to test promptly for WT1 defects in 46,XY gonadal dysgenesis. © 2015 S. Karger AG, Basel
AB - Heterozygous missense mutations in the WT1 gene that affect the function of the wild-type allele have been identified in Denys-Drash syndrome, which is characterized by severe gonadal dysgenesis, early-onset nephropathy and a predisposition to renal and gonadal cancer. Intron 9 splice-site mutations that influence the balance between WT1 isoforms cause a nearly similar phenotype, known as Frasier syndrome. Nonsense mutations and deletions only lead to WT1 haploinsufficiency and, hence, to less severe gonadal dysgenesis and late-onset nephropathy. WT1 analysis is mandatory in 46,XY gonadal dysgenesis with renal abnormality. We describe a newborn with 46,XY severe partial gonadal dysgenesis, in whom structural renal anomalies and proteinuria were excluded. Gonadectomy was performed at the age of 1 month and the microscopy was thought to be suggestive for a gonadoblastoma. At the age of 9 months, the patient presented with a bilateral Wilms tumor. We found a heterozygous WT1 whole-gene deletion but no other gene defects. This case description illustrates that a WT1 deletion might be associated with a more severe phenotype than previously thought. It also illustrates that, even in the absence of renal abnormality, it is recommended to test promptly for WT1 defects in 46,XY gonadal dysgenesis. © 2015 S. Karger AG, Basel
U2 - https://doi.org/10.1159/000368964
DO - https://doi.org/10.1159/000368964
M3 - Article
C2 - 25613702
SN - 1663-2818
VL - 83
SP - 211
EP - 216
JO - Hormone Research in Paediatrics
JF - Hormone Research in Paediatrics
IS - 3
ER -