The clinically and genetically heterogenous foetal akinesias have low rates of genetic diagnosis. Exome sequencing of two siblings with phenotypic lethal multiple pterygium syndrome identified compoun Show more
The clinically and genetically heterogenous foetal akinesias have low rates of genetic diagnosis. Exome sequencing of two siblings with phenotypic lethal multiple pterygium syndrome identified compound heterozygozity for a known splice site mutation (c.691+2T>C) and a novel missense mutation (c.956A>G; p.His319Arg) in glycogen branching enzyme 1 (GBE1). GBE1 mutations cause glycogen storage disease IV (GSD IV), including a severe foetal akinesia sub-phenotype. Re-investigating the muscle pathology identified storage material, consistent with GSD IV, which was confirmed biochemically. This study highlights the power of exome sequencing in genetically heterogeneous diseases and adds multiple pterygium syndrome to the phenotypic spectrum of GBE1 mutation. Show less
Oocyte maturation and early embryonic development require the cytoplasmic polyadenylation and concomitant translational activation of stored maternal mRNAs. ePAB [embryonic poly(A)-binding protein, al Show more
Oocyte maturation and early embryonic development require the cytoplasmic polyadenylation and concomitant translational activation of stored maternal mRNAs. ePAB [embryonic poly(A)-binding protein, also known as ePABP and PABPc1-like] is a multifunctional post-transcriptional regulator that binds to poly(A) tails. In the present study we find that ePAB is a dynamically modified phosphoprotein in Xenopus laevis oocytes and show by mutation that phosphorylation at a four residue cluster is required for oocyte maturation. We further demonstrate that these phosphorylations are critical for cytoplasmic polyadenylation, but not for ePAB's inherent ability to promote translation. Our results provide the first insight into the role of post-translational modifications in regulating PABP protein activity in vivo. Show less