Publications by authors named "E MacNamara"
Article Synopsis
- PI4KA-related disorder is marked by a variety of neurological and gastrointestinal issues, including spasticity, developmental challenges, and recurrent infections, with specific attention given to the impact on B-cell function and immunodeficiency in some patients. * -
- The study involved analyzing 13 patients with PI4KA variants, revealing common traits such as B-cell deficiency and hypogammaglobulinemia, alongside significant changes in B-cell subsets and functioning due to metabolic disruptions. * -
- Findings indicate that mutations in PI4KA lead to disturbances in lipid production and metabolic pathways in B cells, fostering mitochondrial dysfunction and abnormal immune responses, suggesting a critical role of PI4KA in B-cell differentiation and health. *
Article Synopsis
- * The study identifies RNU4-2, a non-coding RNA gene, as a significant contributor to syndromic NDD, revealing a specific 18-base pair region with low variation that includes variants found in 115 individuals with NDD.
- * RNU4-2 is highly expressed in the developing brain, and its variants disrupt splicing processes, indicating that non-coding genes play a crucial role in rare disorders, potentially aiding in the diagnosis of thousands with NDD worldwide.
Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA as a novel syndromic NDD gene.
View Article and Find Full Text PDFBiallelic pathogenic variants in MAP3K20, which encodes a mitogen-activated protein kinase, are a rare cause of split-hand foot malformation (SHFM), hearing loss, and nail abnormalities or congenital myopathy. However, heterozygous variants in this gene have not been definitively associated with a phenotype. Here, we describe the phenotypic spectrum associated with heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
View Article and Find Full Text PDFNascent proteins destined for the cell membrane and the secretory pathway are targeted to the endoplasmic reticulum (ER) either posttranslationally or cotranslationally. The signal-independent pathway, containing the protein TMEM208, is one of three pathways that facilitates the translocation of nascent proteins into the ER. The in vivo function of this protein is ill characterized in multicellular organisms.
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