Cellular and clinical report of new Griscelli syndrome type III cases
Article first published online: 3 OCT 2011
Published 2011. This article is a U.S. Government work and is in the public domain in the USA.
Pigment Cell & Melanoma Research
Volume 25, Issue 1, pages 47–56, January 2012
How to Cite
Westbroek, W., Klar, A., Cullinane, A. R., Ziegler, S. G., Hurvitz, H., Ganem, A., Wilson, K., Dorward, H., Huizing, M., Tamimi, H., Vainshtein, I., Berkun, Y., Lavie, M., Gahl, W. A. and Anikster, Y. (2012), Cellular and clinical report of new Griscelli syndrome type III cases. Pigment Cell & Melanoma Research, 25: 47–56. doi: 10.1111/j.1755-148X.2011.00901.x
- Issue published online: 16 DEC 2011
- Article first published online: 3 OCT 2011
- Accepted manuscript online: 25 AUG 2011 02:43AM EST
- PUBLICATION DATA Received 27 September 2010, revised and accepted for publication 22 August 2011, published online 25 August 2011
- Griscelli syndrome type III;
- tripartite complex
The RAB27A/Melanophilin/Myosin-5a tripartite protein complex is required for capturing mature melanosomes in the peripheral actin network of melanocytes for subsequent transfer to keratinocytes. Mutations in any one member of this tripartite complex cause three forms of Griscelli syndrome (GS), each with distinct clinical features but with a similar cellular phenotype. To date, only one case of GS type III (GSIII), caused by mutations in the Melanophilin (MLPH) gene, has been reported. Here, we report seven new cases of GSIII in three distinct Arab pedigrees. All affected individuals carried a homozygous missense mutation (c.102C>T; p.R35W), located in the conserved Slp homology domain of MLPH, and had hypomelanosis of the skin and hair. We report the first cellular studies on GSIII melanocytes, which demonstrated that MLPH(R35W) causes perinuclear aggregation of melanosomes in melanocytes, typical for GS. Additionally, co-immunoprecipitation assays showed that MLPH(R35W) lost its interaction with RAB27A, indicating pathogenicity of the R35W mutation.