A new article in PNAS from Dr. Susan Baserga’s group describes how biallelic splicing variants in a ribosome assembly factor, RBM28, causes a rare ribosomopathy known as alopecia, neurologic defects, and endocrinopathy (ANE) syndrome. This specific case of ANE syndrome was found in a young Brazilian girl which is the second time this syndrome has been diagnosed- the first cases being found in a few male members of an Arab Moslem family. Common symptoms of this syndrome include severe hair loss, neurological impairment, motor deterioration, and both cranial and neural tissue abnormalities.
In this new publication, the Baserga lab characterizes the first female pediatric ANE syndrome patient. They discover that unlike the previous cases of ANE syndrome that were caused by mutation in the highly conserved ribosomal subunit assembly factor RBM28, this patient with ANE syndrome possesses biallelic pre-mRNA splicing variants at 5’ splice sites of exon 5 (ΔE5) and exon 8 (ΔE8). Using computational and cellular techniques, the group was able to determine that the ΔE5 variant produces an in-frame 31 amino acid deletion, and the ΔE8 variant leads to a premature stop codon. They then used a yeast model to determine that the ΔE5 variant produces a partially functional RBM28 protein while the ΔE8 variant produces a functionally null RBM28 transcript. In the patient, the ΔE5 variant was able to confer life, but the compromised function of RBM28 does not allow for proper physical and neurological development.
The first author of this paper, an MB&B graduate student named Carson Bryant, found this project exciting because not only was the group able to determine the molecular pathogenesis of the patient’s disease, but they also gained insight into how RBM28 functions and how ribosomes are made.
Read the article in PNAS here: https://www.pnas.org/content/118/19/e2017777118