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Pediatr Nephrol. 2017 Jan;32(1):81-89. Epub 2016 Jun 14.

Genotype-phenotype analysis of pediatric patients with WT1 glomerulopathy.

Author information

1
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
2
Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
3
Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea.
4
Department of Pediatrics, Pusan National University Children's Hospital, Yangsan, Korea.
5
Department of Pediatrics, Samsung Medical Center, Seoul, Korea.
6
Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea.
7
Department of Pediatrics, Asan Medical Center, Seoul, Korea.
8
Department of Pediatrics, Konkuk University Hospital, Seoul, Korea.
9
Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
10
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea. cheonghi@snu.ac.kr.
11
Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea. cheonghi@snu.ac.kr.
12
Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. cheonghi@snu.ac.kr.

Abstract

BACKGROUND:

WT1 is one of the genes commonly reported as mutated in children with steroid-resistant nephrotic syndrome (SRNS). We analyzed genotype-phenotype correlations in pediatric SRNS patients with WT1 mutations.

METHODS:

From 2001 to 2015, WT1 mutations were detected in 21 out of 354 children with SRNS by genetic screening (5.9 %). The patients were grouped into missense (n = 11) and KTS splicing (n = 10) mutation groups.

RESULTS:

Nine (82 %) patients with missense mutations presented with congenital/infantile nephrotic syndrome, while 8 (80 %) with KTS splicing mutations presented with childhood-onset SRNS. Progression to end-stage renal disease (ESRD) was noted in all patients with missense mutations (median age, 2.6 months; interquartile range [IQR], 0.8 months to 1.7 years) and in 5 patients with KTS splicing mutations (median, 9.3 years; IQR, 3.3-16.5 years). Disorders of sexual development (DSDs) were noted in all 12 patients with a 46, XY karyotype and in only 1 of the 8 patients with a 46, XX karyotype. One patient developed a Wilms tumor and another developed gonadoblastoma. Three patients had a diaphragmatic defect or hernia.

CONCLUSIONS:

WT1 mutations manifest as a wide spectrum of renal and extra-renal phenotypes. Genetic diagnosis is essential for overall management and to predict the genotype-specific risk of DSDs and the development of malignancies.

KEYWORDS:

Diaphragmatic defect; Disorder of sexual development; Malignancy; Steroid-resistant nephrotic syndrome; WT1 gene

PMID:
27300205
DOI:
10.1007/s00467-016-3395-4
[Indexed for MEDLINE]

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