GRISCELLI syndrome
Griscelli syndrome (GS) is a rare genetic condition
• mature melanosomes transfer to the dendrites tips defects
• Inheritance
autosomal recessive
◊ Type GS:
GS1, GS2, GS3
◊ No partial Albinism form.
The “partial (or incomplete or imperfect)” Albinism term is obsolete.
It was used in the early 900 to denote subjects with ocular albinism abnormalities but with no total absence of skin and hair pigment.
◊ No syndromic Albinism form:
it is not associated with the visual alterations that are characteristic of albinism.
◊ Features (phenotype):
• skin and hair (GS1, GS2, GS3):
pigmentary dilution of the skin
silver-grey hair
melanin clumps within hair shafts
mature melanosomes accumulation in the centre of melanocytes
• neurologic system (GS1)
neurologic abnormalities: developmental delay, mental retardation
• immunologic system (GS2
immunology abnormalities: hemophagocitic syndrome (HS)
◊ Molecular basis (genotype)
Mutations in MYO5A, RAB27A and MLPH genes that encode the MyoVA-Rab27a-Mlph protein complex in melonocytes. This protein complex keeps melanosomes connected to the actin network for mature melanosomes transfer to the tips of the dendrites.
• GS1: mutations in the myosin VA gene (MYO5A), which encodes the myosin VA protein (MyoVA)
MYO5A gene
15q21.2 chr location
MyoVA protein
|
Type |
Gene locus |
Chromosomal localization |
Product |
|
GS1 |
MYO5A |
15q21.2 |
MyoVA protein |
• GS2: :mutations in the Ras-associated protein RAB27A gene (RAB27A), which encodes a small GTPase protein (Rab27a)
RAB27A gene
15q21.3 chr location
Rab27a protein
|
Type |
Gene locus |
Chromosomal localization |
Product |
|
GS2 |
RAB27A |
15q21.3 |
Rab27a protein |
• GS3: mutation in the melanophilin gene (MLPH), which encodes the melanophilin protein (Mlph)
MLPH gene
2q37.3 chr location
Mlph protein
|
Type |
Gene locus |
Chromosomal localization |
Product |
|
GS3 |
MLPH |
2q37.3 |
Mlph protein |
