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http://dx.doi.org/10.1016/j.ajhg.2021.11.013 | DOI Listing |
J Biol Chem
September 2025
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Aminoacyl-tRNA synthetases (aaRSs) catalyze the aminoacylation of tRNA with their cognate amino acids, an essential step in protein biosynthesis. While biallelic mutations in aaRSs often result in severe multi-organ dysfunction accompanied by developmental delays, monoallelic mutations typically cause milder, tissue-specific symptoms. However, a de novo monoallelic nonsense mutation (R534*) in the asparaginyl-tRNA synthetase (AsnRS)-resulting in a premature stop codon and 15-residue C-terminal truncation-has been identified in multiple families and is associated with severe neurodevelopmental symptoms.
View Article and Find Full Text PDFWe recently showed that mutations in and , two genes that are transcribed into small nuclear RNA (snRNA) components of the major spliceosome, are prevalent causes of dominant neurodevelopmental disorders (NDDs). By genetic association comparing 12,776 NDD cases with 56,064 controls, we now demonstrate the existence of a recessive form of syndrome that, in England, is even more common than the dominant form. We inferred log Bayes factors for dominant and recessive models of association of 14.
View Article and Find Full Text PDFBlood Cancer Discov
September 2025
Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Genomic antigen loss is a recurring mechanism of resistance to chimeric antigen receptor T-cell (CAR-T) and T-cell engagers (TCE) in relapsed/refractory multiple myeloma (RRMM). Yet, it remains unclear whether these events are acquired under treatment or merely selected from pre-existing, undetectable clones. By leveraging chemotherapy mutational signatures as temporal barcodes within whole genome sequencing data, we could time genomic antigen escape in 4 out of 11 RRMM patients.
View Article and Find Full Text PDFEur J Pediatr
September 2025
Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
Unlabelled: Enlarged vestibular aqueduct (EVA) is one of the most common inner ear malformations (IEMs) leading to hearing loss in children. Although its genetic and clinical characteristics have been studied, its manifestations in completely deaf children in China, especially those with or without incomplete partition type II (IP-II), are not yet fully understood. We conducted a comprehensive analysis of 123 pediatric EVA children with complete hearing loss.
View Article and Find Full Text PDFNature
September 2025
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK.
Nuclease-helicase DNA2 is a multifunctional genome caretaker that is essential for cell proliferation in a range of organisms, from yeast to human. Bi-allelic DNA2 mutations that reduce DNA2 concentrations cause a spectrum of primordial dwarfism disorders, including Seckel and Rothmund-Thomson-related syndromes. By contrast, cancer cells frequently express high concentrations of DNA2 (refs.
View Article and Find Full Text PDF