Different clinical presentations of WT1 gene mutations
Mustafa Aydin, Nilay Hakan, Aysegul Zenciroglu, Ozlem Aydog & Nurullah Okumus European Journal of Pediatrics ISSN 0340-6199 Eur J Pediatr DOI 10.1007/s00431-013-2085-5
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Author's personal copy Eur J Pediatr DOI 10.1007/s00431-013-2085-5
CORRESPONDENCE
Different clinical presentations of WT1 gene mutations Mustafa Aydin & Nilay Hakan & Aysegul Zenciroglu & Ozlem Aydog & Nurullah Okumus
Received: 5 June 2013 / Accepted: 22 June 2013 # Springer-Verlag Berlin Heidelberg 2013
Dear Editor, We read with great interest the article by Yang et al. [4] who described a child with isolated nephrotic syndrome (NS) and Wilms' tumor suppressor 1 (WT1) gene mutation. The patient presenting as a 46, XY phenotypic male developed end-stage kidney disease (ESKD) at the age of 6.3 years. A mutation, 1051A>G in exon 8 of WT1 gene, has been identified in their patient. Mutations in the WT1 gene may lead to Denys–Drash syndrome (DDS; Online Mendelian Inheritance in Man (OMIM) 194080) or Frasier syndrome (OMIM 136680) and may also cause to isolate NS [4]. Recently, we reported on a novel WT1 gene mutation in a newborn infant diagnosed as DDS [1]. Hence, we would like to make some comments on their report. Denys–Drash syndrome is a rare disorder characterized by glomerulopathy, genital abnormalities, and predisposition to Wilms' tumor. It is associated with constitutional WT1 gene mutations, in which the majority being missense mutations in the zinc-finger DNA-binding region. These mutations occur especially in exons 8 and 9 [3]. WT1 gene encodes different
M. Aydin Division of Neonatology, Department of Pediatrics, Elazig Training and Research Hospital, Elazig, Turkey N. Hakan (*) Division of Neonatology, Department of Pediatrics, Erzurum Training and Research Hospital, Erzurum, Turkey e-mail:
[email protected] A. Zenciroglu : N. Okumus Division of Neonatology, Department of Pediatrics, Dr. Sami Ulus Maternity and Children’s Hospital, Ankara, Turkey O. Aydog Division of Pediatric Nephrology, Department of Pediatrics, Dr. Sami Ulus Maternity and Children’s Hospital, Ankara, Turkey
isoforms of the WT1 protein. The WT1 protein mediates the mesenchymal–epithelial transition and differentiation during morphogenesis of the kidney and gonad by repressing genes that encode cell proliferation factors and by activating genes that encode markers of epithelial cell differentiation [2]. As a consequence, mutations in the WT1 gene result in the loss of its regulatory function. In our case, a novel heterozygous missense mutation, c.1186G>C (p.Asp 396 His), in exon 9 of WT1 gene was identified. The NS became apparent during existence in the first months of life, in contrast to the patient of Yang et al. [4]. The patient was referred to our neonatal intensive care unit because of having ambiguous genitalia, generalized edema, and renal failure by the age of day 20. On laboratory investigations, urinary protein was >1,000 mg/dL with a spot urine protein/creatinine ratio of 33, blood urea nitrogen of 55 mg/dL (3–12), creatinine of 3.5 mg/dL (0.3–1), total protein of 2.2 g/dL (4.6–7.4), and albumin of 1.2 g/dL (2.5–3.5). The glomerular filtration rate was 6.2 mL/min/ 1.73 m2. Karyotype analysis showed a normal male karyotype, 46XY. The abdominal ultrasonography showed bilateral grade 2 increased renal parenchymal echogenicity and a smooth contoured mass with a size of 25×27 mm in the lower pole of the right kidney. Pathological examination of the removed mass showed a stage I neoplastic Wilms' tumor. Renal histopathology was compatible with diffuse mesangial sclerosis, and the patient progressed to ESKD by the age of 95th day [1]. These different clinical manifestations might be explained by various types and localizations of the WT1 gene mutations. Therefore, investigation of the WT1 gene mutations may be helpful in the diagnosis of the patient with NS and rapidly progressed ESKD.
Conflict of interest The authors report that they have no any conflict of interest and any financial relationships.
Author's personal copy Eur J Pediatr
References 1. Hakan N, Aydin M, Erdogan O, Cavusoglu YH, Aycan Z, Ozaltin F, Zenciroglu A, Apaydin S, Gunes R, Sahin G, Cinar G, Okumus N, Hakan N, Aydin M, Erdogan O et al (2012) A novel WT1 gene mutation in a newborn infant diagnosed with Denys-Drash syndrome. Genet Couns 23:255–261
2. Kreidberg JA (2010) WT1 and kidney progenitor cells. Organogenesis 6:61–70 3. Mueller RF (1994) The Denys-Drash syndrome. J Med Genet 31:471–477 4. Yang Y, Feng D, Huang J, Nie X, Yu Z, Yang Y, Feng D, Huang J et al (2013) A child with isolated nephrotic syndrome and WT1 mutation presenting as a 46, XY phenotypic male. Eur J Pediatr 172:127–129
