Griscelli syndrome
Encyclopedia
Griscelli syndrome is a rare autosomal recessive disorder characterized by albinism
(hypopigmentation) with immunodeficiency
, that usually causes death by early childhood.
transport, and divided into several types:
Examination of the hair in this syndrome may be useful. Under light microscopy, these hairs exhibit bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, the hairs appear monotonously white.
In melanocytes, melanosomes (vesicle
s containing the pigment melanin
) are transported on microtubules. They are then bound by Rab27
A which recruits Slac2-a and myosin
Va. This complex then transfers the melanosomes from the microtubules to actin
filaments. This transfer is necessary for the transport of melanosomes from the perinuclear area to the cell periphery. The loss of any one of these proteins interrupts melanosome transport and results in the hypopigmentation.
However, these three proteins do not work together in other cells and Rab27A effectors
may be 'mix and match' For example the knockout of Rab27 causes the hypopigmentation but also immunodeficiency due to deficiencies in cytotoxic killing activity in cytotoxic T cell
s (something that also depends on vesicle
transport). While, the knockout of myosin Va does not cause immunodeficiency, but it does cause neural defects. Though some neural problems (i.e. brain damage) can be seen in Rab27A deficient children, this is thought to be a secondary effect of the immune problems, and not directly due to the lack of Rab27A.
Albinism
Albinism is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin...
(hypopigmentation) with immunodeficiency
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
, that usually causes death by early childhood.
Types
Griscelli syndrome is a disorder of melanosomeMelanosome
In a biological cell, a melanosome is an organelle containing melanin, the most common light-absorbing pigment found in the animal kingdom.Cells that synthesize melanins are called melanocytes, and also the retinal pigment epithelium cells, whereas cells that have merely engulfed the melanosomes...
transport, and divided into several types:
| OMIM | Name | Gene |
|---|---|---|
| Griscelli syndrome type 1 Elejalde syndrome Elejalde syndrome is a rare autosomal recessive syndrome consisting of moderate pigment dilution, profound primary neurologic defects, no immune defects, and hair with metallic silvery sheen.... (Elejalde syndrome) |
MYO5A MYO5A Myosin-Va is a protein that in humans is encoded by the MYO5A gene.-Interactions:MYO5A has been shown to interact with DYNLL1, RAB27A and DYNLL2.-Clinical significance:... |
|
| Griscelli syndrome type 2 Griscelli syndrome type 2 Griscelli syndrome type 2 is a rare autosomal recessive syndrome characterized by variable pigmentary dilution, hair with silvery metallic sheen, frequent pyogenic infections, neutropenia, and thrombocytopenia.-References:... (Partial albinism with immunodeficiency) |
RAB27A RAB27A Ras-related protein Rab-27A is a protein that in humans is encoded by the RAB27A gene.-Interactions:RAB27A has been shown to interact with EXPH5, SYTL1, MYO5A, RPH3AL and SYTL2.-Further reading:... |
|
| Griscelli syndrome type 3 Griscelli syndrome type 3 Griscelli syndrome type 3 is a disorder of melanosome transport presenting initially with hypopigmentation.... |
MLPH |
Presentation
Griscelli syndrome is defined by the characteristic hypopigmentation, with frequent pyogenic infection, hepatosplenomegaly, neutropenia, thrombocytopenia, and immunodeficiency. Very often there is also impaired natural killer cell activity, absent delayed-type hypersensitivity and a poor cell proliferation response to antigenic challenge. This may be caused by the loss of three different genes, each of which has different additional effects, resulting in three types of syndrome. Its Inheritance is autosomal recessive.Examination of the hair in this syndrome may be useful. Under light microscopy, these hairs exhibit bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, the hairs appear monotonously white.
Pathophysiology
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
s containing the pigment melanin
Melanin
Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...
) are transported on microtubules. They are then bound by Rab27
Rab27
Rab27 is a member of the Rab subfamily of GTPases. Rab27 is post translationally modified by the addition of two geranylgeranyl groups on the two C-terminal cysteines.-Pathology:...
A which recruits Slac2-a and myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
Va. This complex then transfers the melanosomes from the microtubules to actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
filaments. This transfer is necessary for the transport of melanosomes from the perinuclear area to the cell periphery. The loss of any one of these proteins interrupts melanosome transport and results in the hypopigmentation.
However, these three proteins do not work together in other cells and Rab27A effectors
Effector (biology)
An effector is a molecule that binds to a protein and thereby alters the activity of that protein...
may be 'mix and match' For example the knockout of Rab27 causes the hypopigmentation but also immunodeficiency due to deficiencies in cytotoxic killing activity in cytotoxic T cell
Cytotoxic T cell
A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...
s (something that also depends on vesicle
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
transport). While, the knockout of myosin Va does not cause immunodeficiency, but it does cause neural defects. Though some neural problems (i.e. brain damage) can be seen in Rab27A deficient children, this is thought to be a secondary effect of the immune problems, and not directly due to the lack of Rab27A.