What is Griscelli Syndrome?
Griscelli Syndrome is a disease that was first characterized by a unique form of albinism and frequent infections. The albinism is characterized by large clumps of pigment in the hair. Individuals with GS presenting with immunodeficiency have a normal number of lymphocytes and yet cannot fight off infections [1,2].
The types of GS are characterized by which specific gene is defective.
The types of GS are characterized by which specific gene is defective.
Type II
Type II is the most common form of GS. Like other forms, type II features partial albinism. Unlike other forms type II lacks signs of neurological deficiency and instead is better characterized by a weakened immune system [3]. Current treatment for type II is a bone marrow transplant.
The Rab27A Gene
Genetic analysis of patients with type II GS showed mutations in the gene Rab27A. The protein encoded by this gene plays a role in exporting cellular products to the outside of the cell [3]. The failure of melanocytes to export pigment outside of the cell explains why patients end up with silvery hair. The immune system issues are explained by failure of immune cells to export components necessary for the lysosome to fight off infections. Mutations in Rab27A show an autosomal recessive pattern of inheritance.
Knowledge Gap
Still unclear are why the symptoms of GS are so specific and seem to mostly involve a few distinct tissues in the body despite RAB27A being expressed globally in the body and exocytosis being an essential process for most cell types.
References
[1] Griscelli et al. A syndrome relating partial albinism and immunodeficiency. Am J Med. 1978 Oct;65(4):691-702.
[2] Klein et al. Partial albinism with immunodeficiency (Griscelli syndrome). J Pediatr. 1994 Dec;125(6 Pt 1):886-95.
[3] Menasche et al. Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nat Genet. Jun;25(2):173-6.
Images
Header: 20190822-tcell_0.jpg
Baby/Hair Follicle: https://ars.els-cdn.com/content/image/1-s2.0-S1110863015001093-gr2.jpg
[1] Griscelli et al. A syndrome relating partial albinism and immunodeficiency. Am J Med. 1978 Oct;65(4):691-702.
[2] Klein et al. Partial albinism with immunodeficiency (Griscelli syndrome). J Pediatr. 1994 Dec;125(6 Pt 1):886-95.
[3] Menasche et al. Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nat Genet. Jun;25(2):173-6.
Images
Header: 20190822-tcell_0.jpg
Baby/Hair Follicle: https://ars.els-cdn.com/content/image/1-s2.0-S1110863015001093-gr2.jpg
The web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison