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Cellular and clinical report of new Griscelli syndrome type III cases.

Authors
  • Westbroek, Wendy
  • Klar, Aharon
  • Cullinane, Andrew R
  • Ziegler, Shira G
  • Hurvitz, Haggit
  • Ganem, Ashraf
  • Wilson, Kirkland
  • Dorward, Heidi
  • Huizing, Marjan
  • Tamimi, Haled
  • Vainshtein, Igor
  • Berkun, Yackov
  • Lavie, Moran
  • Gahl, William A
  • Anikster, Yair
Type
Published Article
Journal
Pigment Cell & Melanoma Research
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jan 01, 2012
Volume
25
Issue
1
Pages
47–56
Identifiers
DOI: 10.1111/j.1755-148X.2011.00901.x
PMID: 21883982
Source
Medline
License
Unknown

Abstract

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.

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