This report describes Shwachman-Diamond syndrome 1 (SDS1); SDS1 exhibits autosomal recessive inheritance. The human gene implicated in this disease encodes SBDS Ribosome Maturation Factor, a highly conserved protein that plays an essential role in ribosome biogenesis. There is a single orthologous gene in Drosophila, Dmel\Sbds, for which a number of genetic reagents have been generated, including RNAi-targeting constructs, alleles caused by insertional mutagenesis, and a targeted CRISPR knockout construct.
A UAS construct of the wild-type human Hsap\SBDS gene has been introduced into flies. Partial heterologous rescue (functional complementation) has been demonstrated: expression of the human gene ameliorates the lethality phenotype of loss-of-function mutations of Dmel\Sbds.
Ubiquitous knockdown of Dmel\Sbds, effected by RNAi, results in lethality at various stages; similar results are observed for homozygous loss-of-function mutations. Pan-neuronal knockdown allows survival to adulthood and results in locomotive disabilities, mechanically-induced seizures, hyperactivity, learning impairments, and anatomical defects in presynaptic terminals.
A postulated example of indirect somatic genetic rescue (SGR) has been investigated in this system, assessing rescue by missense mutations of Dmel\eIF6 on the Sbds loss-of-function lethal phenotype.
[updated Sep. 2021 by FlyBase; FBrf0222196]
[SHWACHMAN-DIAMOND SYNDROME 1; SDS1](https://omim.org/entry/260400)
[SBDS RIBOSOME MATURATION FACTOR; SBDS](https://omim.org/entry/607444)
Shwachman-Diamond syndrome is a multisystem autosomal recessive disorder characterized by exocrine pancreatic dysfunction, bony metaphyseal dysostosis, and varying degrees of marrow dysfunction with cytopenias. Myelodysplastic syndrome and acute myeloid leukemia occur in up to one third of patients (summary by Dror and Freedman, 1999; pubmed:12181037). [from MIM:260400; 2021.01.18]
Shwachman-Diamond syndrome-1 (SDS1) is caused by compound heterozygous or homozygous mutations in the SBDS gene. [from MIM:260400; 2021.01.18]
SBDS encodes a highly conserved protein that plays an essential role in ribosome biogenesis. The SBDS protein is required for the assembly of mature ribosomes and ribosome biogenesis. Together with EFL1, SBDS triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation; required for normal levels of protein synthesis. [Gene Cards, SBDS; 21.01.18]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human SBDS (1 Drosophila to 1 human). Dmel\Sbds shares 59% identity and 74% similarity with the human gene.
