Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-01

AUTHORS

Yo Han Ahn, Eu Jin Park, Hee Gyung Kang, Seong Heon Kim, Hee Yeon Cho, Jae Il Shin, Joo Hoon Lee, Young Seo Park, Kyo Sun Kim, Il-Soo Ha, Hae Il Cheong

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. More... »

PAGES

81-89

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00467-016-3395-4

DOI

http://dx.doi.org/10.1007/s00467-016-3395-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052319392

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27300205


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    "description": "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.\nMETHODS: From 2001 to 2015, WT1 mutations were detected in 21 out of 354 children with SRNS by genetic screening (5.9\u00a0%). The patients were grouped into missense (n\u2009=\u200911) and KTS splicing (n\u2009=\u200910) mutation groups.\nRESULTS: Nine (82\u00a0%) patients with missense mutations presented with congenital/infantile nephrotic syndrome, while 8 (80\u00a0%) 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\u00a0months; interquartile range [IQR], 0.8\u00a0months to 1.7\u00a0years) and in 5 patients with KTS splicing mutations (median, 9.3\u00a0years; IQR, 3.3-16.5\u00a0years). 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.\nCONCLUSIONS: 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.", 
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