Griscelli syndrome (GS, MIM 214450), a rare, autosomal recessive disorder, results in pigmentary dilution of the skin and the hair, the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes. Most patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome (known as haemophagocytic syndrome, HS), leading to death in the absence of bone-marrow transplantation. In contrast, early in life some GS patients show a severe neurological impairment without apparent immune abnormalities. We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients. Further linkage analysis suggested a second gene associated with GS was in the same chromosomal region. Homozygosity mapping in additional families narrowed the candidate region to a 3.1-cM interval between D15S1003 and D15S962. We detected mutations in RAB27A, which lies within this interval, in 16 patients with GS. Unlike MYO5A, the GTP-binding protein RAB27A appears to be involved in the control of the immune system, as all patients with RAB27A mutations, but none with the MYO5A mutation, developed HS. In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not. RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis.

Due to a cloning error, the sequence reported for ING1 was incorrect. The error appears to have been a result of a compression introducing a frameshift and of the ING1 gene encoding several differentially spliced isoforms that contain a common 3′ exon, one of which is of a size very similar to that reported in the publication above. The original (ING1a´, previously called ING1) and the corrected (ING1a) sequences of the isoform of ING1 that was first reported are shown at right (a). The sequence that we reported was frameshifted and truncated at the 5′ end, and we now know that it encodes a protein with a predicted mass of 46,751 rather than the predicted 33,253 daltons. A truncated ING1a message also encodes an expressed protein of 23,656 daltons that results from initiation at the first internal ATG in the conserved exon. An alternatively spliced isoform, ING1b, shares a common 3′ exon with ING1a and encodes a protein with a predicted mass of 31,843 daltons. We now refer to the proteins encoded by this gene as p47 ING1a , p33 ING1b and p24 ING1c due to their relative electrophoretic mobilities. These polypeptides are found in the majority of primary and established tissue culture cells examined, including those of fibroblast, epithelial and glial origin. A schematic diagram of the proteins encoded by the two major transcripts of ING1 are shown (b). All three proteins contain a region with a high degree of homology to PHD fingers that are implicated in transcriptional regulation. The complete, corrected nucleotide sequences for the cDNAs encoding ING1a and-b are available at accession numbers AF181849 (for ING1a, formerly listed as AF001954) and AF181850 at GenBank. We regret any inconvenience that may have resulted from the sequencing error. Expression constructs encoding full-length ING1a, ING1b and ING1c proteins are available from Dongping Ma,

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