Article Text

Download PDFPDF
GDNF as a candidate modifier in a type 1 neurofibromatosis (NF1) enteric phenotype
  1. Michel Bahuau*,a,
  2. Anna Peletb,
  3. Dominique Vidauda,
  4. Thierry Lamireauc,
  5. Brigitte Le Baild,
  6. Arnold Munnichb,
  7. Michel Vidauda,
  8. Stanislas Lyonnetb,
  9. Didier Lacombec
  1. aLaboratoire de Génétique Moléculaire, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris V René-Descartes, 4 Avenue de l'Observatoire, 75006 Paris, France, bUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital Necker Enfants-Malades, Assistance Publique-Hôpitaux de Paris, 149 Rue de Sèvres, 75743 Paris Cedex 15, France, cService de Pédiatrie et Génétique Médicale, Groupe Hospitalier Pellegrin, Centre Hospitalier Universitaire de Bordeaux, 33076 Bordeaux Cedex, France, dLaboratoire d'Anatomie et Cytologie Pathologiques, Groupe Hospitalier Pellegrin, Centre Hospitalier Universitaire de Bordeaux, 33076 Bordeaux Cedex, France
  1. Dr Vidaud,mvidaud{at}teaser.fror Dr Lyonnet,lyonnet{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Editor—Neurofibromatosis type 1 (NF1) is a common human disorder (1/3500 live births) with neuroectodermal involvement primarily resulting in dermatological manifestations of café au lait spots, cutaneous/subcutaneous neurofibromas, and freckling of major skin folds.1 Owing to diagnostic uncertainties, especially in young patients, an international scoring system has been discussed and agreed upon.2 Half of the cases result from new mutations, while others show an autosomal dominant mode of inheritance. The encoded product, referred to as neurofibromin, is a member of the so called GTPase activating proteins (GAPs), and is an upstream downregulator of the RAS(p21)/RAF/MAPkinase3 and RAS/RAL4 signalling pathways. Although locus homogeneity is a hallmark of this condition, phenotypic heterogeneity has been exemplified by a wide spectrum of diversity ranging from malformation or malignant variants to virtually benign dermatological changes.1 In particular, and among the many causes of gastrointestinal involvement in NF1 patients, the association with intrinsic intestinal dysmotility, resulting from intestinal neuronal dysplasia type B (IND B)5 6 or aganglionic megacolon (Hirschsprung's disease, HSCR),7 has been documented and is now well established.

Interestingly, a substantial fraction of the phenotypic variability seen in NF1 patients might be governed by non-allelic, trait specific, “modifying” loci.8 Although the action of such modifying loci has been primarily shown in the number of café au lait spots or the number of cutaneous/subcutaneous neurofibromas, it can be speculated that such a genetic phenomenon might also be operative in other phenotypic traits, especially in individual or familial cases with an enteric phenotype.

The female proband from the family analysed here (fig 1A) had minor cutaneous manifestations of NF1, dysmorphic facial features (midface hypoplasia), congenital heart disease (ventricular septal defect, coarctation of the aorta), and congenital megacolon. She subsequently underwent a Duhamel abdominoperineal pull through and pathological …

View Full Text


  • * Present address: Service de Biochimie et Biologie Moléculaire, Hôpital d'Enfants Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, 75571 Paris Cedex 12, France