Article Text

Mutation analysis of the DKC1 gene in incontinentia pigmenti
  1. NINA S HEISS,
  2. ANNEMARIE POUSTKA
  1. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
  2. Department of Haematology, Imperial College School of Medicine, London, UK
  3. Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  4. Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Texas, Houston, USA
  5. International Institute of Genetics and Biophysics (IIGB), Via G Marconi 10, 80125 Naples, Italy
  6. Hopital des Enfants-Malades, Unité des Recherches sur les Handicaps Génétiques de l’Enfant, Paris, France
  7. Service de Dermatologie, Centre Hospitalier Universitaire, Paris, France
  8. University of Cambridge, Department of Medicine, Cambridge Institute for Medical Research, Cambridge, UK
    1. STUART W KNIGHT
    1. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    2. Department of Haematology, Imperial College School of Medicine, London, UK
    3. Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA
    4. Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Texas, Houston, USA
    5. International Institute of Genetics and Biophysics (IIGB), Via G Marconi 10, 80125 Naples, Italy
    6. Hopital des Enfants-Malades, Unité des Recherches sur les Handicaps Génétiques de l’Enfant, Paris, France
    7. Service de Dermatologie, Centre Hospitalier Universitaire, Paris, France
    8. University of Cambridge, Department of Medicine, Cambridge Institute for Medical Research, Cambridge, UK
      1. SWAROOP ARADHYA,
      2. DAVID L NELSON
      1. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
      2. Department of Haematology, Imperial College School of Medicine, London, UK
      3. Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA
      4. Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Texas, Houston, USA
      5. International Institute of Genetics and Biophysics (IIGB), Via G Marconi 10, 80125 Naples, Italy
      6. Hopital des Enfants-Malades, Unité des Recherches sur les Handicaps Génétiques de l’Enfant, Paris, France
      7. Service de Dermatologie, Centre Hospitalier Universitaire, Paris, France
      8. University of Cambridge, Department of Medicine, Cambridge Institute for Medical Research, Cambridge, UK
        1. RICHARD A LEWIS
        1. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
        2. Department of Haematology, Imperial College School of Medicine, London, UK
        3. Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA
        4. Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Texas, Houston, USA
        5. International Institute of Genetics and Biophysics (IIGB), Via G Marconi 10, 80125 Naples, Italy
        6. Hopital des Enfants-Malades, Unité des Recherches sur les Handicaps Génétiques de l’Enfant, Paris, France
        7. Service de Dermatologie, Centre Hospitalier Universitaire, Paris, France
        8. University of Cambridge, Department of Medicine, Cambridge Institute for Medical Research, Cambridge, UK
          1. TERESA ESPOSITO,
          2. ALFREDO CICCODICOLA,
          3. MICHELE D’URSO
          1. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
          2. Department of Haematology, Imperial College School of Medicine, London, UK
          3. Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA
          4. Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Texas, Houston, USA
          5. International Institute of Genetics and Biophysics (IIGB), Via G Marconi 10, 80125 Naples, Italy
          6. Hopital des Enfants-Malades, Unité des Recherches sur les Handicaps Génétiques de l’Enfant, Paris, France
          7. Service de Dermatologie, Centre Hospitalier Universitaire, Paris, France
          8. University of Cambridge, Department of Medicine, Cambridge Institute for Medical Research, Cambridge, UK
            1. ASMAE SMAHI,
            2. SOLANGE HEUERTZ,
            3. ARNOLD MUNNICH
            1. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
            2. Department of Haematology, Imperial College School of Medicine, London, UK
            3. Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA
            4. Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Texas, Houston, USA
            5. International Institute of Genetics and Biophysics (IIGB), Via G Marconi 10, 80125 Naples, Italy
            6. Hopital des Enfants-Malades, Unité des Recherches sur les Handicaps Génétiques de l’Enfant, Paris, France
            7. Service de Dermatologie, Centre Hospitalier Universitaire, Paris, France
            8. University of Cambridge, Department of Medicine, Cambridge Institute for Medical Research, Cambridge, UK
              1. PIERRE VABRES
              1. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
              2. Department of Haematology, Imperial College School of Medicine, London, UK
              3. Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA
              4. Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Texas, Houston, USA
              5. International Institute of Genetics and Biophysics (IIGB), Via G Marconi 10, 80125 Naples, Italy
              6. Hopital des Enfants-Malades, Unité des Recherches sur les Handicaps Génétiques de l’Enfant, Paris, France
              7. Service de Dermatologie, Centre Hospitalier Universitaire, Paris, France
              8. University of Cambridge, Department of Medicine, Cambridge Institute for Medical Research, Cambridge, UK
                1. HAYLEY WOFFENDIN,
                2. SUSAN KENWRICK
                1. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
                2. Department of Haematology, Imperial College School of Medicine, London, UK
                3. Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA
                4. Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Texas, Houston, USA
                5. International Institute of Genetics and Biophysics (IIGB), Via G Marconi 10, 80125 Naples, Italy
                6. Hopital des Enfants-Malades, Unité des Recherches sur les Handicaps Génétiques de l’Enfant, Paris, France
                7. Service de Dermatologie, Centre Hospitalier Universitaire, Paris, France
                8. University of Cambridge, Department of Medicine, Cambridge Institute for Medical Research, Cambridge, UK

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                  Editor—There are a number of monogenic diseases with complex phenotypes which are clinically distinct but also overlap in phenotype with one or more other syndromes. If mutations in the same gene are responsible for causing the related syndromes, the diseases are allelic. Two diseases linked to Xq28, incontinentia pigmenti (IP, MIM 308310, Bloch-Sulzberger syndrome) and dyskeratosis congenita (DKC, MIM 305000, Zinsser-Cole-Engmann syndrome) show similarities in phenotype, although the modes of expression differ. Whereas IP is X linked dominant with embryonic lethality in males, the major form of DKC is X linked recessive. The gene responsible for causing DKC,DKC1, was recently identified1and maps about 20 kb proximal to the factor VIII gene,F8C. 2 Linkage analyses have provided evidence that the IP gene is located in the telomeric 2 Mb region of Xq28 distal to DXS523 and lod scores of highest significance were found aroundF8C. 4 5 The physical map position of DKC1 and genetic linkage of the IP locus, together with the overlap in the DKC and IP phenotypes (table1), raised the possibility that these two diseases could be allelic.

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                  Table 1

                  Comparison of the IP and DKC phenotypes affecting ectodermal tissues and the haemopoietic system

                  The IP and DKC phenotypes share abnormalities in ectodermal derivatives, such as nail dystrophy, alopecia, hypodontia, and skin manifestations6 7 (table 1). Both IP and DKC are characterised by the early appearance of reticulate skin pigmentation, although this manifests differently in the two diseases. In IP the clinical signs affecting the skin are initially apparent as an erythematous, inflammatory vesicular rash. The rash later becomes verrucous and streaks of hyperpigmentation follow. …

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