Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10

Authors

  • Veronique Pingault,

    Corresponding author
    1. Hôpital Henri Mondor, AP-HP, Laboratoire de Biochimie et Génétique, Créteil, France
    2. INSERM, U955, Equipe 11, Créteil, France
    3. Université Paris Est, UMR_S955, UPEC, Créteil, France
    • Correspondence to:

      Veronique Pingault, IMRB (Inserm U955), Equipe 11, Hopital Henri Mondor, 94010 Creteil Cedex, France.

      E-mail: veronique.pingault@inserm.fr

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  • Laurence Pierre-Louis,

    1. Maison de la Femme de la Mère et de l'Enfant (MFME), Service de Réanimation, de Soins Intensifs Néonatals et de Néonatologie, CHU Martinique, Fort-de-France
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  • Asma Chaoui,

    1. INSERM, U955, Equipe 11, Créteil, France
    2. Université Paris Est, UMR_S955, UPEC, Créteil, France
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  • Alain Verloes,

    1. Department of Genetics, APHP-Robert Debre University Hospital, Paris VII-Denis Diderot University, INSERM U676, Paris, France
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  • Elisabeth Sarrazin,

    1. Centre de Référence Caribéen des Maladies Rares Neuromusculaires et Neurologiques Adultes et Enfant, CERCA, Hôpital Pierre Zobda Quitman, CHU Martinique, Fort-de-France
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  • Goran Brandberg,

    1. Pediatric and Adolescent Clinic, County Hospital, Falun, Sweden
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  • Nadege Bondurand,

    1. INSERM, U955, Equipe 11, Créteil, France
    2. Université Paris Est, UMR_S955, UPEC, Créteil, France
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  • Peter Uldall,

    1. Pediatric and Adolescent Clinic, The Juliane Marie Centre, Rigshospitalet, University Hospital, Copenhagen, Denmark
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  • Sylvie Manouvrier-Hanu

    1. Service de Génétique Clinique, Centre Hospitalo-Universitaire de Lille, Lille, France
    2. Faculté de Médecine, Université Lille 2, Lille, France
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  • The authors declare no conflict of interest.

Abstract

Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype–phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype–phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. © 2014 Wiley Periodicals, Inc.

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