ArticleAmerican journal of human genetics2016
Autosomal-Recessive Mutations in the tRNA Splicing Endonuclease Subunit TSEN15 Cause Pontocerebellar Hypoplasia and Progressive Microcephaly.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Mapping the Diverse Genetic Disorders and Rare Diseases Among the Syrian Population: Implications on Refugee Health and Health Services in Host Countries.Journal of immigrant and minority health · 2020Pooled it
- Polyglycine-mediated aggregation of FAM98B disrupts tRNA processing in GGC repeat disorders.Science (New York, N.Y.) · 2025Article
- Exploring the Potential of tsRNA as Biomarkers for Diagnosis and Treatment of Neurogenetic Disorders.Molecular neurobiology · 2025Review
- Pontocerebellar hypoplasia: a review from 1912 to 2022.Brain communications · 2025Review
- Evaluation of the Patients with the Diagnosis of Pontocerebellar Hypoplasia: A Multicenter National Study.Cerebellum (London, England) · 2024Article
- tRNA Modifications and Dysregulation: Implications for Brain Diseases.Brain sciences · 2024Review
- Space radiation damage rescued by inhibition of key spaceflight associated miRNAs.Nature communications · 2024Article
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
- Recognition and cleavage mechanism of intron-containing pre-tRNA by human TSEN endonuclease complex.Nature communications · 2023Article
- The life and times of a tRNA.RNA (New York, N.Y.) · 2023Review
- An unknown essential function of tRNA splicing endonuclease is linked to the integrated stress response and intron debranching.Genetics · 2023Article
- Rodent Models of Audiogenic Epilepsy: Genetic Aspects, Advantages, Current Problems and Perspectives.Biomedicines · 2022Review
- tRNA dysregulation and disease.Nature reviews. Genetics · 2022Review
- The tRNA regulome in neurodevelopmental and neuropsychiatric disease.Molecular psychiatry · 2022Review
- Mutations in Drosophila tRNA processing factors cause phenotypes similar to Pontocerebellar Hypoplasia.Biology open · 2022Article
- A splice site mutation in the TSEN2 causes a new syndrome with craniofacial and central nervous system malformations, and atypical hemolytic uremic syndrome.Clinical genetics · 2022Article
- Novel compound heterozygous variant of TOE1 results in a mild type of pontocerebellar hypoplasia type 7: an expansion of the clinical phenotype.Neurogenetics · 2022Article
- Diagnostic Approach to Cerebellar Hypoplasia.Cerebellum (London, England) · 2021Review
- Three-Dimensional X-ray Imaging of β-Galactosidase Reporter Activity by Micro-CT: Implication for Quantitative Analysis of Gene Expression.Brain sciences · 2021Article
- Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1.European journal of human genetics : EJHG · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
The tRNA splicing endonuclease is a highly evolutionarily conserved protein complex, involved in the cleavage of intron-containing tRNAs. In human it consists of the catalytic subunits TSEN2 and TSEN34, as well as the non-catalytic TSEN54 and TSEN15. Recessive mutations in the corresponding genes of the first three are known to cause pontocerebellar hypoplasia (PCH) types 2A-C, 4, and 5. Here, we report three homozygous TSEN15 variants that cause a milder version of PCH2. The affected individuals showed progressive microcephaly, delayed developmental milestones, intellectual disability, and, in two out of four cases, epilepsy. None, however, displayed the central visual failure seen in PCH case subjects where other subunits of the TSEN are mutated, and only one was affected by the extensive motor defects that are typical in other forms of PCH2. The three amino acid substitutions impacted the protein level of TSEN15 and the stoichiometry of the interacting subunits in different ways, but all resulted in an almost complete loss of in vitro tRNA cleavage activity. Taken together, our results demonstrate that mutations in any known subunit of the TSEN complex can cause PCH and progressive microcephaly, emphasizing the importance of its function during brain development.
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