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Involvement of SOX10 in the pathogenesis of Hirschsprung disease: report of a truncating mutation in an isolated patient

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Abstract

SOX10 protein is a key transcription factor during neural crest development. Mutations in SOX10 are associated with several neurocristopathies such as Waardenburg syndrome type IV (WS4), a congenital disorder characterized by the association of hearing loss, pigmentary abnormalities, and absence of ganglion cells in the myenteric and submucosal plexus of the gastrointestinal tract, also known as aganglionic megacolon or Hirschsprung disease (HSCR). Several mutations at this locus are known to cause a high percentage of WS4 cases, but no SOX10 mutations had been ever reported associated to isolated HSCR patient. Therefore, nonsyndromic HSCR was initially thought not to be associated to mutations at this particular locus. In the present study, we describe the evaluation of the SOX10 gene in a series of 196 isolated HSCR cases, the largest patient series evaluated so far, and report a truncating c.153–155del mutation. This is the first time that a SOX10 mutation is detected in an isolated HSCR patient, which completely changes the scenario for the implications of SOX10 mutations in human disease, giving us a new tool for genetic counseling.

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Acknowledgments

We would like to thank all the patients who participated in the study as well as their families for their collaboration. This study was funded by Fondo de Investigación Sanitaria, Spain (PI070080 and PI071315 for the E-Rare project) and Consejeria de Innovación Ciencia y Empresa (CTS 2590). The CIBER de Enfermedades Raras is an initiative of the ISCIII. ASM is predoctoral fellow founded by Instituto de Salud Carlos III, Spain.

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None.

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Authors and Affiliations

  1. Unidad de Gestión Clínica de Genética, Reproducción y Medicina Fetal, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013, Seville, Spain

    Avencia Sánchez-Mejías, Raquel M. Fernández, Guillermo Antiñolo & Salud Borrego

  2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Seville, Spain

    Avencia Sánchez-Mejías, Raquel M. Fernández, Manuel López-Alonso, Guillermo Antiñolo & Salud Borrego

  3. INSERM, Unité U955, Créteil, France

    Yuli Watanabe & Nadege Bondurand

  4. Faculté de Médecine, Université Paris 12, Créteil, France

    Yuli Watanabe & Nadege Bondurand

  5. Unidad de Gestión Clínica de Cirugía Infantil, Hospital Universitario Virgen del Rocío, Seville, Spain

    Manuel López-Alonso

Authors
  1. Avencia Sánchez-Mejías
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  2. Yuli Watanabe
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  3. Raquel M. Fernández
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  4. Manuel López-Alonso
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  5. Guillermo Antiñolo
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  6. Nadege Bondurand
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  7. Salud Borrego
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Corresponding author

Correspondence to Salud Borrego.

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Supplementary Table 1

PCR primers and conditions for mutational screening. TaH and TiH are hybridization temperature and hybridization time for PCR, respectively, in the general conditions: (95°C-300 s)–[(95°C-30 s)–(TaH-TiH)–(72°C-30 s)] × 35–(72°C-420 s). (DOC 41 kb)

Supplementary Table 2

QMF-PCR primer sequences. PCR conditions were as follow: (95°C-600 s)→[(92°C-15 s)→(60°C-60 s)] × 40. (DOC 39 kb)

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Sánchez-Mejías, A., Watanabe, Y., M. Fernández, R. et al. Involvement of SOX10 in the pathogenesis of Hirschsprung disease: report of a truncating mutation in an isolated patient. J Mol Med 88, 507–514 (2010). https://doi.org/10.1007/s00109-010-0592-7

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  • DOI: https://doi.org/10.1007/s00109-010-0592-7

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