Griscelli syndrome is a rare autosomal recessive^[1] disorder characterized by albinism (hypopigmentation) with immunodeficiency, that usually causes death by early childhood. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Albinism (from Latin albus, "white" see extended etymology) is a form of hypopigmentary Congenital disorder, In Medicine, immunodeficiency (or immune deficiency) is a state in which the Immune system 's ability to fight Infectious disease is compromised

Types

• Type I Griscelli syndrome -- MYO5A
• Type II Griscelli syndrome is caused by the knock out of the gene for Rab27A and is characterised by hypopigmentation and immunodeficiency. Myosin VA (heavy chain 12 myoxin, also known as MYO5A, is a human Gene. 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 Children with this syndrome die with a mean age of 5 years. The only cure is bone-marrow transplantation. To date approximately 10 children have received successful bone marrow transplants for type II Griscelli syndrome.
• Type III Griscelli syndrome -- melanophilin, MYO5A

Presentation

Griscelli syndrome is defined by the characteristic hypopigmentation. Melanophilin is a Carrier protein which links Rab27a Myosin VA (heavy chain 12 myoxin, also known as MYO5A, is a human Gene. This may be caused by the loss of three different genes, each of which has different additional effects, resulting in the three types of syndrome.

Pathophysiology

Griscelli syndrome has an autosomal recessive pattern of inheritance. "Heir" and "Heiress" redirect here For the men and women fragrances endorsed by Paris Hilton see Heiress (fragrance.

In melanocytes, melanosomes (vesicles containing the pigment melanin) are transported on microtubules. In a biological cell, a melanosome is an Organelle containing Melanin, the most common light-absorbing pigment found in the animal kingdom Melanin is a class of compounds found in the Plant, Animal and Protista kingdoms, where it serves predominantly as a Pigment. Microtubules are one of the components of the Cytoskeleton. They have a diameter of 25 nm and length varying from 200 nanometers to 25 micrometers They are then bound by Rab27A which recruits Slac2-a and myosin Va. 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 Melanophilin is a Carrier protein which links Rab27a Myosins are a large family of Motor proteins found in Eukaryotic tissues. This complex then transfers the melanosomes from the microtubules to actin filaments. Actin is a globular roughly 42-kDa Protein found in all eukaryotic cells (except for Nematode sperm where it may be present at concentrations of 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 cells (something that also depends on vesicle transport). An effector is a molecule (originally referring to small molecules but now encompassing any regulatory molecule includes proteins that binds to a Protein and thereby alters A cytotoxic T cell (also known as TC, CTL T-Killer cell cytolytic T cell CD8+ T-cells or killer T cell) belongs to a sub-group of T lymphocytes 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.

Eponym

It is named for Claude Griscelli. ^[2][3]

References