Link: http://www.ncbi.nlm.nih.gov/pubmed/27300205

Pediatr Nephrol. 2016 Jun 14. [Epub ahead of print]
Genotype-phenotype analysis of pediatric patients with WT1 glomerulopathy.
Ahn YH1,2, Park EJ1, Kang HG1,3, Kim SH4, Cho HY5, Shin JI6, Lee JH7, Park YS7, Kim KS8, Ha IS1,9, Cheong HI10,11,12.
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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 [PubMed - as supplied by publisher]