Rapp–Hodgkin syndrome and the tail of p63

Authors

  • I. Chan,

    1. Genetic Skin Disease Group, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, London, UK, and the Department of Medical Genetics, The Family Federation of Finland, Helsinki, Finland
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  • J. A. McGrath,

    1. Genetic Skin Disease Group, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, London, UK, and the Department of Medical Genetics, The Family Federation of Finland, Helsinki, Finland
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  • S. Kivirikko

    1. Genetic Skin Disease Group, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, London, UK, and the Department of Medical Genetics, The Family Federation of Finland, Helsinki, Finland
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J. A. McGrath, Genetic Skin Disease Group, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, London, UK.
E-mail: john.mcgrath@kcl.ac.uk

Summary

We report the clinical and molecular abnormalities in a 19-year-old woman with Rapp–Hodgkin ectodermal dysplasia syndrome. The physical features include mid-facial hypoplasia, uncombable hair, cleft palate and bifid uvula, lacrimal duct obstruction and dry skin. Sequencing of the p63 gene reveals a new heterozygous frameshift mutation, 1787delG, in exon 14. The frameshift results in changes to the tail of p63 with the addition of 68 missense amino acids downstream and a delayed termination codon that extends the protein length by 21 amino acids. These changes are predicted to disrupt the normal repressive function of the transactivation inhibitory domain leading to gain-of-function for at least two isoforms of the p63 transcription factor. The expanding p63 mutation database demonstrates that there is overlap between Rapp–Hodgkin syndrome and several other ectodermal dysplasia syndromes, notably Hay–Wells syndrome, and that characterization of the functional consequences of these p63 gene mutations at a molecular and cellular level is likely to provide further insight into the clinical spectrum of these developmental malformation syndromes.

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