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Chaouch A, Porcelli V, Cox D, et al. Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. J Neuromuscul Dis. 2014;1(1):75-90doi: 10.3233/JND-140021.
Chaouch, A., Porcelli, V., Cox, D., Edvardson, S., Scarcia, P., De Grassi, A., Pierri, C. L., Cossins, J., Laval, S. H., Griffin, H., Müller, J. S., Evangelista, T., Töpf, A., Abicht, A., Huebner, A., von der Hagen, M., Bushby, K., Straub, V., Horvath, R., Elpeleg, O., Palace, J., Senderek, J., Beeson, D., Palmieri, L., & Lochmüller, H. (2014). Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. Journal of neuromuscular diseases, 1(1), 75-90. https://doi.org/10.3233/JND-140021
Chaouch, Amina, et al. "Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission." Journal of neuromuscular diseases vol. 1,1 (2014): 75-90. doi: https://doi.org/10.3233/JND-140021
Chaouch A, Porcelli V, Cox D, Edvardson S, Scarcia P, De Grassi A, Pierri CL, Cossins J, Laval SH, Griffin H, Müller JS, Evangelista T, Töpf A, Abicht A, Huebner A, von der Hagen M, Bushby K, Straub V, Horvath R, Elpeleg O, Palace J, Senderek J, Beeson D, Palmieri L, Lochmüller H. Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. J Neuromuscul Dis. 2014;1(1):75-90. doi: 10.3233/JND-140021. PMID: 26870663; PMCID: PMC4746751.
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J Neuromuscul Dis. 2014;1(1):75-90. doi: 10.3233/JND-140021.

Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission.

Journal of neuromuscular diseases

Amina Chaouch, Vito Porcelli, Daniel Cox, Shimon Edvardson, Pasquale Scarcia, Anna De Grassi, Ciro L Pierri, Judith Cossins, Steven H Laval, Helen Griffin, Juliane S Müller, Teresinha Evangelista, Ana Töpf, Angela Abicht, Angela Huebner, Maja von der Hagen, Kate Bushby, Volker Straub, Rita Horvath, Orly Elpeleg, Jacqueline Palace, Jan Senderek, David Beeson, Luigi Palmieri, Hanns Lochmüller

Affiliations

  1. Institute of Genetic Medicine, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne, UK.
  2. Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari Aldo Moro, Bari, Italy.
  3. Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
  4. Neurosciences Group, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, UK.
  5. Medizinisch Genetisches Zentrum, Munich, Germany ; Friedrich-Baur-Institut, Ludwig Maximilians University, Munich, Germany.
  6. Children's Hospital, Technical University Dresden, Dresden, Germany.
  7. Department of Clinical Neurology, The John Radcliffe, Oxford, UK.
  8. Friedrich-Baur-Institut, Ludwig Maximilians University, Munich, Germany.
  9. Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari Aldo Moro, Bari, Italy ; CNR Institute of Biomembranes and Bioenergetics, Bari, Italy.

PMID: 26870663 PMCID: PMC4746751 DOI: 10.3233/JND-140021

Abstract

BACKGROUND AND OBJECTIVE: Congenital myasthenic syndromes are rare inherited disorders characterized by fatigable weakness caused by malfunction of the neuromuscular junction. We performed whole exome sequencing to unravel the genetic aetiology in an English sib pair with clinical features suggestive of congenital myasthenia.

METHODS: We used homozygosity mapping and whole exome sequencing to identify the candidate gene variants. Mutant protein expression and function were assessed

RESULTS: We identified a novel homozygous missense mutation in the

CONCLUSIONS: Based on the axonal outgrowth defects seen in SLC25A1 knockdown zebrafish, we hypothesize that the neuromuscular junction impairment may be related to pre-synaptic nerve terminal abnormalities. Our findings highlight the complex machinery required to ensure efficient neuromuscular function, beyond the proteomes exclusive to the neuromuscular synapse.

Keywords: Congenital myasthenic syndrome; SLC25A1; mitochondrial citrate carrier; neuromuscular junction

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