Molecular Characteristics
DDX59 is located at 1q32.1 and encodes a DEAD box-containing RNA helicase that is involved in unwinding double-stranded RNA and in RNA metabolism, including splicing, nuclear export, and ribosomal biogenesis. Additionally, DDX59 has been shown to be involved in ciliary SHH signalling. DDX59 is highly enriched in the lips, secondary palate, and developing limb buds of developing mice. Additionally, it has been recently found to be highly expressed in the brain, particularly in the white matter. At the cellular level, immunofluorescence using DDX59 antibody has shown granular cytoplasmic and dynamic nuclear localization, which may suggest a diverse role in RNA biology.
Mutations and pathophysiology
Shamseldin et al. identified homozygosity for two different missense mutations in two different families: c.1100T>G, p.(Val367Gly), in the first family and c.1600G>A, p.(Gly534Arg) in the second. p.(Val367Gly) has been found to affect a highly conserved ATP-binding domain, whereas p.(Gly534Arg) affects a highly conserved helicase domain.
Faily et al. identified c.1859G > T, p.(*620Leuext*22), affecting a stop codon resulting in an extended protein product.
Salpietro et al. identified a homozygous frameshift deletion, c.185del, p.(Phe62fs*13), causing premature truncation of the protein and a more severe phenotype with a complex heterogeneous neurological involvement.
In addition to disrupting RNA metabolism by DEAD box-containing RNA helicases, mutations in DDX59 also appear to impair ciliary SHH signalling. Salpietro et al. has also shown that mahe (Drosophila ortholog of DDX59) null embryos showed highly disorganized neuron clusters and axonal projections, loss or incomplete ventral nerve cord, and shortened lifespan.