Griscelli
syndrome (GS) is a rare autosomal recessive disorder caused by
mutation in the MYO5A (GS1, Elejalde), RAB27A (GS2) or MLPH (GS3)
genes. Typical features of all three subtypes of this
disease include pigmentary
dilution of the
hair and
skin and silvery-gray
hair. Whereas the GS3
phenotype is restricted to the
pigmentation dysfunction, GS1
patients also show primary neurological impairment and GS2
patients have severe immunological deficiencies that
lead to
recurrent infections and
hemophagocytic syndrome. We
report here the
diagnosis of GS2 in 3-year-old
twin siblings, with silvery-gray
hair, immunodeficiency, hepatosplenomegaly and
secondary severe neurological symptoms that culminated in
multiple organ failure and
death.
Light microscopy examination of the
hair showed large, irregular clumps of pigments characteristic of GS. A homozygous
nonsense mutation, C-T transition (c.550C>T), in the
coding region of the RAB27A
gene, which leads to a
premature stop codon and prediction of a truncated
protein (R184X), was found. In
patient mononuclear
cells, RAB27A
mRNA levels were the same as in
cells from the
parents, but no
protein was detected. In addition to the case
report, we also present an updated summary on the
exon/
intron organization of the
human RAB27A
gene, a literature review of GS2 cases, and a complete list of the
human mutations currently reported in this
gene. Finally, we propose a flow chart to guide the
early diagnosis of the GS subtypes and
Chédiak-Higashi syndrome.