The SBDS gene is expressed in all tissues and encodes a protein of 250 amino acid residues. A great deal of indirect evidence suggested that the SBDS protein may be involved in an aspect of cellular RNA metabolism or ribosome assembly or function. The wide occurrence of the gene in all archaea and eukaryotes supported a role for this protein in a very fundamental and evolutionarily conserved aspect of cellular biology. The homologous genes in archaea also tend to be present in conserved cluster enriched for RNA processing and ribosomal genes. A specific function for SBDS in RNA metabolism or ribosome assembly or function is further supported by its localization to the nucleolus, the nuclear subdomain where these processes occur. In line with this, the yeast homologue, SdoI, has been shown to be critical for maturation of pre-60S ribosomes, by effecting release and recycling of the nucleolar shuttling factor Tif6. This is required for 60S maturation and translational activation of ribosomes. It has also been shown that the Dictyostelium discoideum homologue catalyzes the removal of eukaryotic initiation factor 6 (eIF6), which is required for the translational activation of ribosomes. Cells from SDS patients were shown to have a defect in assembly of ribosome subunits. At present, it is not obvious how disruption of the basic cellular process of translation leads to the tissue- and organ-specific manifestations seen in SDS. However, unusual and combinations of tissues and organs are also affected in<unk> –Blackfan anemia, X-linked dyskeratosis congenita, and cartilage–hair hypoplasia—three diseases that may also be linked to defective ribosome function. Pleiotropic disease features may be the result of cell-specific effects of reduced levels of SBDS activity provided by hypomorphic mutations.
Shwachman–Diamond syndrome
Wilson–Turner syndrome
Foix–Alajouanine syndrome
Wilson–Mikity syndrome
Rubinstein–Taybi syndrome
Laurence–Moon syndrome
Crigler–Najjar syndrome
Wiedemann–Steiner syndrome