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Motility and visceral sensation
Analysis of the RET,GDNF, EDN3, andEDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease
  1. R Gath†,a,
  2. A Goessling†,a,
  3. K-M Kellerb,
  4. S Koletzkoc,
  5. W Coerdtd,
  6. H Münteferingd,
  7. S Wirthe,
  8. R M W Hofstraf,
  9. L Mulligang,
  10. C Engh,
  11. A von Deimlingi
  1. aDepartment of Neuropathology, University of Bonn Medical Centre, D-53105 Bonn, Germany, bDeutsche Klinik für Diagnostik, D-65191 Wiesbaden, Germany, cDepartment of Paediatrics, University of Munich, D-80336 Munich, Germany, dDepartment of Paediatric Pathology, University of Mainz Medical Centre, D-55101 Mainz, Germany, eChildren's Hospital, D-42283 Wuppertal, Germany, fDepartment of Medical Genetics, University of Groningen, 9713aw Groningen, Netherlands, gDepartment of Pediatrics, Queen's University, Kingston, ON K7L 3N6, Canada, hClinical Cancer Genetics and Human Cancer Genetics Programs, Comprehensive Cancer Center, and Division of Human Genetics, Department of Internal Medicine, Ohio State University, Columbus, OH, USA; Cancer Research Campaign Human Cancer Genetics Research Group, University of Cambridge, Cambridge, UK, iDepartment of Neuropathology, Charité, Humboldt University, D-13353 Berlin, Germany
  1. Dr A von Deimling, Institut für Neuropathologie, Charité, Campus Virchow Klinikum, Augustenburgerplatz 1, D-13353 Berlin, Germany.andreas.von_deimling{at}charite.de Accepted for publication 19 December 2000

Abstract

BACKGROUND Hirschsprung disease (HSCR) is a frequent congenital disorder with an incidence of 1 in 5000 live births, characterised by the absence of parasympathetic intramural ganglion cells in the hindgut resulting in intestinal obstruction in neonates and severe constipation in infants and adults. Intestinal neuronal dysplasia (IND) shares clinical features with HSCR but the submucosal parasympathetic plexus is affected. IND has been proposed as one of the most frequent causes of chronic constipation and is often associated with HSCR.

METHODS We examined 29 patients diagnosed with sporadic HSCR, 20 patients with IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of theRET, GDNF,EDNRB, and EDN3genes. The entire coding regions were analysed by single strand conformational polymorphism and DNA sequencing.

RESULTS Only threeRET mutations were detected in patients with HSCR. In patients with IND or a mixed HSCR/IND phenotype, no mutations in these genes were observed. While HSCR and HSCR/IND showed over representation of a specific RET polymorphism in exon 2, IND exhibited a significantly lower frequency comparable with that of controls.

CONCLUSIONS The mutation frequency found in our sporadic HSCR patients (10%) and the allelic distribution of RET polymorphisms are comparable with earlier published data. A significantly different allelic distribution in an established HSCR associated polymorphism argues against common genetic pathways for HSCR and IND.

  • Hirschsprung disease
  • intestinal neuronal dysplasia
  • RET
  • GDNF
  • EDNRB
  • EDN3

  • Abbreviations used in this paper

    IND
    intestinal neuronal dysplasia
    HSCR
    Hirschsprung disease
    SSCP
    single strand conformational polymorphism

    • https://doi.org/10.1136/gut.48.5.671

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    • Abbreviations used in this paper

      IND
      intestinal neuronal dysplasia
      HSCR
      Hirschsprung disease
      SSCP
      single strand conformational polymorphism
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