Journal article
Authors list: Heiman, Guy; Mendes, Marisa, I; Nicita, Francesco; Darbelli, Lama; Sherbini, Omar; Moore, Travis; Derksen, Alexa; Pizzino, Amy; Carrozzo, Rosalba; Torraco, Alessandra; Catteruccia, Michela; Aiello, Chiara; Goffrini, Paola; Figuccia, Sonia; Smith, Desiree E. C.; Hadzsiev, Kinga; Hahn, Andreas; Biskup, Saskia; Broesse, Ines; Kotzaeridou, Urania; Gauck, Darja; Grebe, Theresa A.; Elmslie, Frances; Stals, Karen; Gupta, Rajat; Bertini, Enrico; Thiffault, Isabelle; Taft, Ryan J.; Schiffmann, Raphael; Brandl, Ulrich; Haack, Tobias B.; Salomons, Gajja S.; Simons, Cas; Bernard, Genevieve; van der Knaap, Marjo S.; Vanderver, Adeline; Husain, Ralf A.
Publication year: 2021
Pages: 2352-2359
Journal: Genetics in Medicine
Volume number: 23
Issue number: 12
ISSN: 1098-3600
eISSN: 1530-0366
Open access status: Bronze
DOI Link: https://doi.org/10.1038/s41436-021-01286-8
Publisher: Elsevier
Abstract:
Purpose Recent reports of individuals with cytoplasmic transfer RNA (tRNA) synthetase-related disorders have identified cases with phenotypic variability from the index presentations. We sought to assess phenotypic variability in individuals with AARS1-related disease. Methods A cross-sectional survey was performed on individuals with biallelic variants in AARS1. Clinical data, neuroimaging, and genetic testing results were reviewed. Alanyl tRNA synthetase (AlaRS) activity was measured in available fibroblasts. Results We identified 11 affected individuals. Two phenotypic presentations emerged, one with early infantile-onset disease resembling the index cases of AARS1-related epileptic encephalopathy with deficient myelination (n = 7). The second (n = 4) was a later-onset disorder, where disease onset occurred after the first year of life and was characterized on neuroimaging by a progressive posterior predominant leukoencephalopathy evolving to include the frontal white matter. AlaRS activity was significantly reduced in five affected individuals with both early infantile-onset and late-onset phenotypes. Conclusion We suggest that variants in AARS1 result in a broader clinical spectrum than previously appreciated. The predominant form results in early infantile-onset disease with epileptic encephalopathy and deficient myelination. However, a subgroup of affected individuals manifests with late-onset disease and similarly rapid progressive clinical decline. Longitudinal imaging and clinical follow-up will be valuable in understanding factors affecting disease progression and outcome.
Citation Styles
Harvard Citation style: Heiman, G., Mendes, M., Nicita, F., Darbelli, L., Sherbini, O., Moore, T., et al. (2021) Expanded phenotype of AARS1-related white matter disease, Genetics in Medicine, 23(12), pp. 2352-2359. https://doi.org/10.1038/s41436-021-01286-8
APA Citation style: Heiman, G., Mendes, M., Nicita, F., Darbelli, L., Sherbini, O., Moore, T., Derksen, A., Pizzino, A., Carrozzo, R., Torraco, A., Catteruccia, M., Aiello, C., Goffrini, P., Figuccia, S., Smith, D., Hadzsiev, K., Hahn, A., Biskup, S., Broesse, I., ...Husain, R. (2021). Expanded phenotype of AARS1-related white matter disease. Genetics in Medicine. 23(12), 2352-2359. https://doi.org/10.1038/s41436-021-01286-8
Keywords
RNA SYNTHETASE MUTATIONS
