Cellular and clinical report of new Griscelli syndrome type III cases

Autor: Kirkland Wilson, Yair Anikster, Haggit Hurvitz, Heidi Dorward, Wendy Westbroek, Moran Lavie, William A. Gahl, Marjan Huizing, Haled Tamimi, Andrew R. Cullinane, Yackov Berkun, Igor Vainshtein, Shira G. Ziegler, Aharon Klar, Ashraf Ganem
Rok vydání: 2011
Předmět:
Zdroj: Pigment Cell & Melanoma Research. 25:47-56
ISSN: 1755-1471
DOI: 10.1111/j.1755-148x.2011.00901.x
Popis: 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 (SHD) 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.
Databáze: OpenAIRE