Advertisement

Pediatric Nephrology

, Volume 19, Issue 10, pp 1160–1163 | Cite as

A novel mutation of WT1 exon 9 in a patient with Denys-Drash syndrome and pyloric stenosis

  • Min Hu
  • Jonathon Craig
  • Neville Howard
  • Alex Kan
  • Jeffrey Chaitow
  • Dianne Little
  • Stephen I. AlexanderEmail author
Brief Report

Abstract

We report a novel mutation in WT1 exon 9 (1214 A>G) resulting in an amino acid change from H to R at codon 405 in a 46 XY female patient who had congenital hypertrophic pyloric stenosis, pseudohermaphroditism masculinus, renal failure, and Wilms tumor, and died at the age of 22 months. The patient demonstrated the difficulty in diagnosing a patient with intersex before conclusive genetic characterization.

Keywords

Denys-Drash syndrome Frasier syndrome Missense mutation Wilms tumor 

References

  1. 1.
    Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, Jones C, Housman DE (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 60:509–520CrossRefPubMedGoogle Scholar
  2. 2.
    Armstrong JF, Pritchard-Jones K, Bickmore WA, Hastie ND, Bard JB (1993) The expression of the Wilms’ tumour gene, WT1 , in the developing mammalian embryo. Mech Dev 40:85–97CrossRefPubMedGoogle Scholar
  3. 3.
    Drash A, Sherman F, Hartmann WH, Blizzard RM (1970) A syndrome of pseudohermaphroditism, Wilms’ tumor, hypertension, and degenerative renal disease. J Pediatr 76:585–593PubMedGoogle Scholar
  4. 4.
    Frasier S, Bashore R, Mosllur H (1964) Gonadoblastoma associated with pure gonadal dysgenesis in monozygotic twins. J Pediatr 64:740–745PubMedGoogle Scholar
  5. 5.
    Angulo JC, Lopez JI, Ereno C, Flores N (1991) Congenital mesoblastic nephroma, nephrocalcinosis, and hypertrophic pyloric stenosis. J Surg Oncol 48:142–144PubMedGoogle Scholar
  6. 6.
    Atwell JD, Levick P (1981) Congenital hypertrophic pyloric stenosis and associated anomalies in the genitourinary tract. J Pediatr Surg 16:1029–1035PubMedGoogle Scholar
  7. 7.
    Mills M, Yang N, Weinberger R, Vander Woude DL, Beggs AH, Easteal S, North K (2001) Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy. Hum Mol Genet 10:1335–1346CrossRefPubMedGoogle Scholar
  8. 8.
    Little M, Wells C (1997) A clinical overview of WT1 gene mutations. Hum Mutat 9:209–225CrossRefGoogle Scholar
  9. 9.
    Jeanpierre C, Denamur E, Henry I, Cabanis MO, Luce S, Cecille A, Elion J, Peuchmaur M, Loirat C, Niaudet P, Gubler MC, Junien C (1998) Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database. Am J Hum Genet 62:824–833CrossRefPubMedGoogle Scholar
  10. 10.
    Schumacher V, Scharer K, Wuhl E, Altrogge H, Bonzel KE, Guschmann M, Neuhaus TJ, Pollastro RM, Kuwertz-Broking E, Bulla M, Tondera AM, Mundel P, Helmchen U, Waldherr R, Weirich A, Royer-Pokora B (1998) Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations. Kidney Int 53:1594–1600CrossRefPubMedGoogle Scholar
  11. 11.
    Dharnidharka VR, Ruteshouser EC, Rosen S, Kozakewich H, Harris HW Jr, Herrin JT, Huff V (2001) Pulmonary dysplasia, Denys-Drash syndrome and Wilms’ tumor 1 gene mutation in twins. Pediatr Nephrol 16:227–231CrossRefPubMedGoogle Scholar
  12. 12.
    Swiatecka-Urban A, Mokrzycki MH, Kaskel F, Da Silva F, Denamur E (2001) Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome. Pediatr Nephrol 16:627–630CrossRefPubMedGoogle Scholar
  13. 13.
    Barbaux S, Niaudet P, Gubler MC, Grunfeld JP, Jaubert F, Kuttenn F, Fekete CN, Souleyreau-Therville N, Thibaud E, Fellous M, McElreavey K (1997) Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet 17:467–470PubMedGoogle Scholar
  14. 14.
    Nishiwaki K, Niikawa N, Ishikawa M (1997) Polymorphic and tissue-specific imprinting of the human Wilms’ tumor gene, WT1. Jpn J Hum Genet 42:205–211PubMedGoogle Scholar
  15. 15.
    Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68:820–823PubMedGoogle Scholar

Copyright information

© IPNA 2004

Authors and Affiliations

  • Min Hu
    • 1
  • Jonathon Craig
    • 1
  • Neville Howard
    • 2
  • Alex Kan
    • 3
  • Jeffrey Chaitow
    • 4
  • Dianne Little
    • 5
  • Stephen I. Alexander
    • 1
    • 6
    Email author
  1. 1.Centre for Kidney Research, Department of NephrologyThe Children’s Hospital at WestmeadAustralia
  2. 2.Institute of Endocrinology and DiabetesThe Children’s Hospital at WestmeadAustralia
  3. 3.Department of PathologyThe Children’s Hospital at WestmeadAustralia
  4. 4.Department of RheumatologyThe Children’s Hospital at WestmeadAustralia
  5. 5.Department of Forensic MedicineICPMRWestmeadAustralia
  6. 6.Centre for Kidney Research, The Department of NephrologyThe Children’s Hospital at WestmeadWestmeadAustralia

Personalised recommendations