Griscelli Syndrome Type 3 (GS Restricted to Hypopigmentation)
Clinical Features and Genetic Patterns
|Photo courtesy of Pigment International Opens in new window|
GS3, the third form of GS Opens in new window, is characterized by the fair skin at birth of CHH and the other forms of GS followed by bronzed skin after sun exposure.
Children can be referred because of unspecific complaints of failure to gain weight or recurrent tonsillitis and then noticed to have silver-gray hair, eyebrows, and eyelashes.
Clinically, GS3-associated albinism is indistinguishable from that described in the other forms of GS.
Skin biopsy and light microscopic examination reveals the same pattern as GS1 Opens in new window and GS2 Opens in new window.
Microscopic analysis of hair shafts show the characteristic features of GS, i.e., the presence of large clumps of pigment in the hair shaft.
Most importantly, longitudinal follow-up reveals that phenotypic presentation is restricted to hypopigmentation, without any immune or neurological manifestation.
GS3 is caused by mutations Opens in new window in the gene that encodes melanophilin (Mlph) (SLAC2A/MLPH gene), the orthologue of the gene mutated in leaden mice.
It has also been shown that an identical phenotype can result from the deletion of the MYOVA F-exon, an exon with a tissue-restricted expression pattern.
The protein Mlph links the function of myosin Va and the GTP-Rab27 a protein in the melanosome without additional functions: this explains why expression in GS3 is restricted to the characteristic hypopigmentation.
In GS3 the Mlph is unable to associate with Rab27a, either transiently over expressed or endogenously expressed in melanocytes.
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