Mutations in DARS Cause Hypomyelination with Brain Stem and Spinal Cord Involvement and Leg Spasticity
| العنوان: | Mutations in DARS Cause Hypomyelination with Brain Stem and Spinal Cord Involvement and Leg Spasticity |
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| المؤلفون: | Stephen A. Damiani, Petra J. W. Pouwels, Joanna Crawford, Truus E.M. Abbink, Paul J. Lockhart, Prab Prabhakar, Ishwar Chander Verma, Ryan J. Taft, Tena Rosser, Nicole I. Wolf, Kate Pope, Cas Simons, Irenaeus F.M. de Coo, David Miller, Adeline Vanderver, Richard J. Leventer, Marjo S. van der Knaap, Susan Blaser, Monica Juneja, Marianna R. Bevova, Julian Raiman, Kelin Ru, Johanna L. Schmidt, Sean M. Grimmond |
| المساهمون: | Other departments, Physics and medical technology, Human genetics, Pediatric surgery, NCA - Brain mechanisms in health and disease, Functional Genomics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Neurology |
| المصدر: | American journal of human genetics, 92(5), 774-780. Cell Press Taft, R J, Vanderver, A, Leventer, R J, Damiani, S A, Simons, C, Grimmond, S M, Miller, D, Schmidt, J, Lockhart, P J, Pope, K, Ru, K L, Crawford, J, Rosser, T, de Coo, I F M, Juneja, M, Verma, I C, Prabhakar, P, Blaser, S, Raiman, J, Pouwels, P J W, Bevova, M R, Abbink, G E M, van der Knaap, M S & Wolf, N I 2013, ' Mutations in DARS Cause Hypomyelination with Brain Stem and Spinal Cord Involvement and Leg Spasticity ', American journal of human genetics, vol. 92, no. 5, pp. 774-780 . https://doi.org/10.1016/j.ajhg.2013.04.006 Taft, R J, Vanderver, A, Leventer, R J, Damiani, S A, Simons, C, Grimmond, S M, Miller, D, Schmidt, J, Lockhart, P J, Pope, K, Ru, K L, Crawford, J, Rosser, T, de Coo, I F M, Juneja, M, Verma, I C, Prabhakar, P, Blaser, S, Raiman, J, Pouwels, P J W, Bevova, M R, Abbink, G E M, van der Knaap, M S & Wolf, N I 2013, ' Mutations in DARS Cause Hypomyelination with Brain Stem and Spinal Cord Involvement and Leg Spasticity ', American Journal of Human Genetics, vol. 92, no. 5, pp. 774-780 . https://doi.org/10.1016/j.ajhg.2013.04.006 American Journal of Human Genetics, 92(5), 774-780. Cell Press |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Nonsynonymous substitution, Models, Molecular, Pathology, medicine.medical_specialty, Protein Conformation, Aspartate-tRNA Ligase, Biology, medicine.disease_cause, Crystallography, X-Ray, Leukoencephalopathy, Leukoencephalopathies, Report, medicine, Genetics, Humans, Genetics(clinical), Spasticity, Gene, Genetics (clinical), Exome sequencing, Mutation, Leg, Molecular pathology, Spinal cord, medicine.disease, medicine.anatomical_structure, Spinal Cord, Muscle Spasticity, medicine.symptom, Brain Stem |
| الوصف: | Inherited white-matter disorders are a broad class of diseases for which treatment and classification are both challenging. Indeed, nearly half of the children presenting with a leukoencephalopathy remain without a specific diagnosis. Here, we report on the application of high-throughput genome and exome sequencing to a cohort of ten individuals with a leukoencephalopathy of unknown etiology and clinically characterized by hypomyelination with brain stem and spinal cord involvement and leg spasticity (HBSL), as well as the identification of compound-heterozygous and homozygous mutations in cytoplasmic aspartyl-tRNA synthetase (DARS). These mutations cause nonsynonymous changes to seven highly conserved amino acids, five of which are unchanged between yeast and man, in the DARS C-terminal lobe adjacent to, or within, the active-site pocket. Intriguingly, HBSL bears a striking resemblance to leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate (LBSL), which is caused by mutations in the mitochondria-specific DARS2, suggesting that these two diseases might share a common underlying molecular pathology. These findings add to the growing body of evidence that mutations in tRNA synthetases can cause a broad range of neurologic disorders. © 2013 The American Society of Human Genetics. |
| اللغة: | English |
| تدمد: | 0002-9297 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21dab9446353b93d11aef5f6fbd9ddb3 https://hdl.handle.net/1871.1/8eeab4b7-6d75-4184-b6f6-2fd306fd4437 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....21dab9446353b93d11aef5f6fbd9ddb3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00029297 |
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