Genotype-phenotype analysis of pediatric patients with WT1 glomerulopathy.
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.



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.



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.



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.
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
Yo Han
YH
Ahn
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
Eu Jin
EJ
Park
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea.
Hee Gyung
HG
Kang
Department of Pediatrics, Pusan National University Children's Hospital, Yangsan, Korea.
Seong Heon
SH
Kim
Department of Pediatrics, Samsung Medical Center, Seoul, Korea.
Hee Yeon
HY
Cho
Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea.
Jae Il
JI
Shin
Department of Pediatrics, Asan Medical Center, Seoul, Korea.
Joo Hoon
JH
Lee
Department of Pediatrics, Asan Medical Center, Seoul, Korea.
Young Seo
YS
Park
Department of Pediatrics, Konkuk University Hospital, Seoul, Korea.
Kyo Sun
KS
Kim
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Il-Soo
IS
Ha
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea. cheonghi@snu.ac.kr.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea. cheonghi@snu.ac.kr.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. cheonghi@snu.ac.kr.
Hae Il
HI
Cheong
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D012734:Disorders of Sex Development / Q000235:genetics / Q000473:pathology; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D005921:Glomerulonephritis / Q000235:genetics* / Q000473:pathology; D018238:Gonadoblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D056910:Republic of Korea; D016019:Survival Analysis; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics / Q000473:pathology
D025721:WT1 Proteins
Diaphragmatic defect; Disorder of sexual development; Malignancy; Steroid-resistant nephrotic syndrome; WT1 gene