SOX10 mutations in patients with Waardenburg-Hirschsprung disease

Véronique Pingault, Nadège Bondurand, Kirsten Kuhlbrodt, Derk E. Goerich, Marie Odette Préhu, Aldamaria Puliti, Beate Herbarth, Irm Hermans-Borgmeyer, Eric Legius, Gert Matthijs, Jeanne Amiel, Stanislas Lyonnet, Isabella Ceccherini, Giovanni Romeo, Jill Clayton Smith, Andrew P. Read, Michael Wegner, Michel Goossens

Research output: Contribution to journalArticlepeer-review


Waardenburg syndrome (WS; deafness with pigmentary abnormalities) and Hirschsprung's disease (HSCR; aganglionic megacolon) are congenital disorders caused by defective function of the embryonic neural crest1,2. WS and HSCR are associated in patients with Waardenburg-Shah syndrome (WS4), whose symptoms are reminiscent of the white coat-spotting and aganglionic megacolon displayed by the mouse mutants Dom (Dominant megacolon), piebald-lethal (s(l)) and lethal spotting (ls). The s(l) and ls phenotypes are caused by mutations in the genes encoding the Endothelin-B receptor (Ednrb) and Endothelin 3 (Edn3), respectively. The identification of Sox10 as the gene mutated in Dom mice (B.H. et al., manuscript submitted) prompted us to analyse the role of its human homologue SOX10 in neural crest defects. Here we show that patients from four families with WS4 have mutations in SOX10, whereas no mutation could be detected in patients with HSCR alone. These mutations are likely to result in haploinsufficiency of the SOX10 product. Our findings further define the locus heterogeneity of Waardenburg- Hirschsprung syndromes, and point to an essential role of SOX10 in the development of two neural crest-derived human cell lineages.

Original languageEnglish
Pages (from-to)171-173
Number of pages3
JournalNature Genetics
Issue number2
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Genetics


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