WT1 gene mutation in exone 7 in boy with disturbance of the sex formation and the bilateral nephroblastoma
https://doi.org/10.21508/1027-4065-2019-64-6-94-97
Abstract
The case of observing a patient with WT1 gene mutation in exone 7 with bilateral Wilms metachronous tumor, disturbance of the sex formation in the form of scrotal hypospadias and bilateral abdominal cryptorchidism, without nephropathy, is presented. The child underwent surgical operations: left-sided nephrectomy, resection of the lower pole of the right kidney, bilateral orchiopexy and two-stage hypospadias correction. 7 years after the start of treatment and 3 years after the final operation, the condition of the child was estimated as satisfactory. The presented case by the results of the molecular genetic study has no previously described analogues and requires further observation.
About the Authors
N. R. Akramov
Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan; Kazan State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Kazan
I. V. Osipova
Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
Russian Federation
Russian Federation
Kazan
A. M. Zakirova
Kazan State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Kazan
E. I. Khaertdinov
Kazan State Medical University of the Ministry of Health of the Russian Federation; Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
Russian Federation
Russian Federation
Kazan
E. L. Rashitova
Kazan State Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Kazan
References
1. National Wilms’ Tumor Study Committee. Wilms’ tumor: status report, 1990. J Clin Oncol 1991; 9: 877–887. DOI: 10.1200/JCO.1991.9.5.877
2. Stefan D.C. Patterns of distribution of childhood cancer in Africa. J Trop Pediatr 2015; 61(3): 165–173. DOI: 10.1093/tropej/fmv005
3. Kulyova S.A., Imyanitov E.N. Wilm’s Tumor: Syndrome-based and Molecular Diagnostics. Onkopediatriya 2017; 4(4): 283–289 (in Russ.) DOI: 10.15690/onco.v4i4.1814.
4. Ward E., DeSantis C., Robbins A., Kohler B., Jemal A. Childhood and Adolescent Cancer Statistics, 2014. Cancer J Clin 2014; 64: 83–103. DOI: 10.3322/caac.21219
5. Green D.M. The treatment of stages I–IV favorable histology Wilms’ tumor. J Clin Oncol 2004; 22(8): 1366–1372. DOI: 10.1200/JCO.2004.08.008
6. Weirich A., Ludwig R., Graf N., Abel U., Leuschner I., Vujanic G.M. et al. Survival in nephroblastoma treated according to the trial and study SIOP-9/GPOH with respect to relapse and morbidity. Ann Oncol 2004; 15: 808–820. DOI: 10.1093/annonc/mdh171
7. Denys P., Malvaux P., van den Berghe H., Tanghe W., Proesmans W. Association d’un syndrome anatomo-pathologique de pseudohermaphrodisme masculin, d’une tumeur de Wilms, d’une nephropathie parenchymateuse et d’un mosaicisme XX/XY. Arch Franc Pediat 1967; 24: 729–739.
8. Drash A., Sherman F., Hartmann W.H., Blizzard R.M. A syndrome of pseudohermaphroditism, Wilms’ tumor, hypertension, and degenerative renal disease. J Pediat 1970; 76: 585– 593. DOI: 10.1016/s0022-3476(70)80409-7
9. Frasier S.D., Bashore R.A., Mosier H.D. Gonadoblastoma associated with pure gonadal dysgenesis in monozygotic twins. J Pediat 1964; 64: 740-745. DOI: 10/1016/s0022-2476(64)80622-3
10. Miller R.W., Fraumeni J.F.Jr., Manning M.D. Association of Wilms’ tumor with aniridia, hemihypertrophy and other congenital malformations. New Eng J Med 1964; 270: 922–927. DOI: 10.1056/NEJM196404302701802
11. Bruening W., Bardeesy N., Silverman B.L., Cohn R.A., Machin G.A., Aronson A.J. et al. Germline intronic and exonic mutations in the Wilms’ tumour gene (WT1) affecting urogenital development. Nat Genet 1992; 1(2): 144–148. DOI: 10.1038/ng0592-144
12. Auber F., Lortat-Jacob S., Sarnacki S., Jaubert F., Salomon R., Thibaud E. et al. Surgical management and genotype/phenotype correlations in WT1 gene-related diseases (Drash, Frasier syndromes). J Pediatr Surg 2003; 38(1): 124–129. DOI: 10.1053/jpsu.2003.50025
13. Takata A., Kikuchi H., Fukuzawa R., Ito S., Honda M., Hata J. Constitutional WT1 correlate with clinical features in children with progressive nephropathy. J Med Genet 2000; 37(9): 698–701. DOI: 10.1136/jmg.37.9.698
14. da Silva T.E., Nishi M.Y., Costa E.M., Martin R.M., Carvalho F.M., Mendonca B.B., Domenice S. A novel WT1 heterozygous nonsense mutation (p.K248X) causing a mild and slightly progressive nephropathy in a 46,XY patient with Denys–Drash syndrome. Pediatr Nephrol 2011; 26(8): 1311–1315. DOI: 10.1007/s00467-011-1847-4
15. Fukuzawa R., Sakamoto J., Heathcott R.W., Hata J.I. A necropsy case of Denys–Drash syndrome with a WT1 mutation in exon 7. J Med Genet 2002; 39(8):e48. DOI: 10.1136/jmg.39.8.e48
16. Jeanpierre C., Béroud C., Niaudet P., Junien C. Software and database for the analysis of mutations in the human WT1 gene. Nucleic Acids Res 1998; 26(1): 271–274. DOI: 10.1093/nar/26.1.271
17. Little M., Wells C. A clinical overview of WT1 gene mutations. Hum Mutat 1997; 9(3): 209–225. DOI: 10.1002/(SICI)1098-1004(1997)9:3<209::AID-HUMU2>3.0.CO;2-2
18. Bardeesy N., Zabel B., Schmitt K., Pelletier J. WT1 mutations associated with incomplete Denys–Drash syndrome define a domain predicted to behave in a dominant-negative fashion. Genomics 1994; 21(3): 663–664. DOI: 10.1006/geno.1994.1333
19. Weaver J., Rove K.O., Meenakshi-Sundaram B., Vricella G.J. Genetic testing proves crucial in case of ambiguous genitalia and renal masses. Urology 2019; 125: 194–196. DOI: 10.1016/j.urology.2019.03.011
20. Chiang P.W., Aliaga S., Travers S., Spector E., Tsai A.C. Case report: WT1 exon 6 truncation mutation and ambiguous genitalia in a patient with Denys–Drash syndrome. Curr Opin Pediatr 2008; 20(1): 103–106. DOI: 10.1097/MOP/0b013e-3282f357eb
21. Lehnhardt A., Karnatz C., Ahlenstiel-Grunow T., Benz K., Benz M.R., Budde K. et al. Clinical and molecular characterization of patients with heterozygous mutations in Wilms tumor suppressor gene 1. Clin J Am Soc Nephrol 2015; 10(5): 825–831. DOI: 10.2215/CJN.10141014
22. Dattolo P., Allinovi M., Iatropoulos P., Michelassi S. Atypical clinical presentation of a WT1-related syndrome associated with a novel exon 6 gene mutation. BMJ Case Rep 2013; 27; 2013. DOI: 10.1136/bcr-2013-009543
23. Finken M.J., Hendriks Y.M, van der Voorn J.P., Veening M.A., Lombardi M.P., Rotteveel J. WT1 deletion leading to severe 46, XY gonadal dysgenesis, Wilms tumor and gonadoblastoma: case report. Horm Res Paediatr 2015; 83(3): 211–216. DOI: 10.1159/000368964
24. Köhler B., Biebermann H., Friedsam V., Gellermann J., Maier R.F., Pohl M. et al. Analysis of the Wilms’ tumor suppressor gene (WT1) in patients 46,XY disorders of sex development. J Clin Endocrinol Metab 2011; 96: E1131–E1136. DOI: 10.1210/jc.2010-2804
Review
For citations:
Akramov N.R., Osipova I.V., Zakirova A.M., Khaertdinov E.I., Rashitova E.L. WT1 gene mutation in exone 7 in boy with disturbance of the sex formation and the bilateral nephroblastoma. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2019;64(6):94-97. (In Russ.) https://doi.org/10.21508/1027-4065-2019-64-6-94-97
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