Original Investigation

Human Genetics

, Volume 111, Issue 2, pp 198-206

SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism

  • Véronique PingaultAffiliated withINSERM U468, Génétique Moléculaire et Physiopathologie, and Laboratoire de Biochimie, Hôpital Henri Mondor, 94010 Créteil Cedex, France
  • , Mathilde GirardAffiliated withINSERM U468, Génétique Moléculaire et Physiopathologie, and Laboratoire de Biochimie, Hôpital Henri Mondor, 94010 Créteil Cedex, France
  • , Nadège BondurandAffiliated withINSERM U468, Génétique Moléculaire et Physiopathologie, and Laboratoire de Biochimie, Hôpital Henri Mondor, 94010 Créteil Cedex, France
  • , Huw DorkinsAffiliated withSt. Peter's College, University of Oxford, and Oxford Clinical Genetics Service, Oxford, United Kingdom
  • , Lionel Van MaldergemAffiliated withCentre de Génétique Humaine, Institut de Pathologie et de Génétique, Loverval, Belgium
  • , David MowatAffiliated withDepartment of Medical Genetics and Pediatrics, Sydney Children's Hospital, University of New South Wales, Sydney, Australia
  • , Takashi ShimotakeAffiliated withDivision of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan
  • , Ishwar VermaAffiliated withDepartment of Genetic Medicine, Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India
  • , Clarisse BaumannAffiliated withU.F. de génétique clinique, hôpital Robert-Debré, Paris, France
    • , Michel GoossensAffiliated withINSERM U468, Génétique Moléculaire et Physiopathologie, and Laboratoire de Biochimie, Hôpital Henri Mondor, 94010 Créteil Cedex, France

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Abstract.

The type IV Waardenburg syndrome (WS4), also referred to as Shah-Waardenburg syndrome or Waardenburg-Hirschsprung disease, is characterised by the association of Waardenburg features (WS, depigmentation and deafness) and the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease). Mutations in the EDN3, EDNRB, and SOX10 genes have been reported in this syndrome. Recently, a new SOX10 mutation was observed in a girl with a neural crest disorder without evidence of depigmentation, but with severe constipation due to a chronic intestinal pseudo-obstruction and persistence of enteric ganglia. To refine the nosology of WS, we studied patients with typical WS4 (including Hirschsprung disease) or with WS and intestinal pseudo-obstruction. We found three SOX10 mutations, one EDNRB and one EDN3 mutations in patients presenting with the classical form of WS4, and two SOX10 mutations in patients displaying chronic intestinal pseudo-obstruction and WS features. These results show that chronic intestinal pseudo-obstruction may be a manifestation associated with WS, and indicate that aganglionosis is not the only mechanism underlying the intestinal dysfunction of patients with SOX10 mutations.