Griscelli disease maps to chromosome 15q21 and is associated with mutations in the Myosin-Va gene (original) (raw)

Nature Genetics volume 16, pages 289–292 (1997)Cite this article

A Correction to this article was published on 01 November 1999

Abstract

Griscelli disease (OMIM 214450) is a rare autosomal recessive disorder characterized by pigmentary dilution, variable cellular immunodeficiency and onset of acute phases of uncontrolled lymphocyte and macrophage activation, leading to death in the absence of bone-marrow transplantation1,2. The pigmentary dilution is characterized by a diffuse skin pigmentation, silvery hair, large clumps of pigment in the hair shafts (Fig. 1) and an accumulation of melanosomes in melanocytes, with abnormal transfer of the melanin granules to the keratinocytes1,3. Immunological abnormalities are characterized by absent delayed-type cutaneous hypersensitivity and an impaired natural-killer cell function1,3. A similar disorder has been described in the dilute lethal mouse4—which, however, differs by the occurrence of a severe neurological disorder. The dilute locus encodes myosin-Va5, a member of the unconventional myosin family. Myosins bind actin and produce mechanical force through ATP hydrolysis. Some members of this family are thought to participate in organelle-transport machinery6. Because of the phenotype resulting in the dilute mouse and because of their potential role in intracellular transport, unconventional myosin-encoding genes were regarded as candidate genes for Griscelli disease. Here we report that the Griscelli disease locus co-localizes on chromosome 15q21 with the myosin-Va gene, MYO5a, and that mutations of this gene occur in two patients with the disease. Griscelli disease is therefore a human equivalent of dilute expression in the mouse.

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Authors and Affiliations

  1. Unité de Recherches sur le Dévelopement Normal et Pathologique du Système Immunitaire INSERM U429, 149 rue de Sèvres, 75743, Paris, Cedex 15, France
    Elodie Pastural, Franck J. Barrat, Rémi Dufourcq-Lagelouse, Stéphanie Certain, Alain Fischer & Geneviève de Saint Basile
  2. Hacettepe Children's Hospital, Ankara, Turkey
    Ozden Sanal
  3. Unité d'Immunologie et d'Hématologie Pédiatrique, Hôpital Necker-Enfants Malades, 149 rue de Sè;vres, 75743, Paris, Cedex 15, France
    Nada Jabado, Claude Griscelli & Alain Fischer
  4. Abteilung Immunologie/Hämatologie, Univ-Kinderspital Zürich, 8032, Zurich, Switzerland
    Reinhard Seger

Authors

  1. Elodie Pastural
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  2. Franck J. Barrat
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  3. Rémi Dufourcq-Lagelouse
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  4. Stéphanie Certain
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  5. Ozden Sanal
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  6. Nada Jabado
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  7. Reinhard Seger
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  8. Claude Griscelli
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  9. Alain Fischer
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  10. Geneviève de Saint Basile
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Correspondence toGeneviève de Saint Basile.

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Pastural, E., Barrat, F., Dufourcq-Lagelouse, R. et al. Griscelli disease maps to chromosome 15q21 and is associated with mutations in the Myosin-Va gene.Nat Genet 16, 289–292 (1997). https://doi.org/10.1038/ng0797-289

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