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Homozygous mutations in VAMP 1 cause a presynaptic congenital myasthenic syndrome
We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusi...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
John Wiley and Sons Inc.
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413866/ https://www.ncbi.nlm.nih.gov/pubmed/28253535 http://dx.doi.org/10.1002/ana.24905 |
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| author | Salpietro, Vincenzo Lin, Weichun Vedove, Andrea Delle Storbeck, Markus Liu, Yun Efthymiou, Stephanie Manole, Andreea Wiethoff, Sarah Ye, Qiaohong Saggar, Anand McElreavey, Kenneth Krishnakumar, Shyam S. Pitt, Matthew Bello, Oscar D. Rothman, James E. Basel‐Vanagaite, Lina Hubshman, Monika Weisz Aharoni, Sharon Manzur, Adnan Y. Wirth, Brunhilde Houlden, Henry |
| author_facet | Salpietro, Vincenzo Lin, Weichun Vedove, Andrea Delle Storbeck, Markus Liu, Yun Efthymiou, Stephanie Manole, Andreea Wiethoff, Sarah Ye, Qiaohong Saggar, Anand McElreavey, Kenneth Krishnakumar, Shyam S. Pitt, Matthew Bello, Oscar D. Rothman, James E. Basel‐Vanagaite, Lina Hubshman, Monika Weisz Aharoni, Sharon Manzur, Adnan Y. Wirth, Brunhilde Houlden, Henry |
| author_sort | Salpietro, Vincenzo |
| collection | PubMed |
| description | We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1 (lew/lew) mice, observing neurophysiological features of presynaptic impairment, similar to the patients. Taken together, our findings highlight VAMP1 homozygous mutations as a cause of presynaptic CMS. Ann Neurol 2017;81:597–603 |
| format | Online Article Text |
| id | pubmed-5413866 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | John Wiley and Sons Inc. |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-54138662017-05-19 Homozygous mutations in VAMP 1 cause a presynaptic congenital myasthenic syndrome Salpietro, Vincenzo Lin, Weichun Vedove, Andrea Delle Storbeck, Markus Liu, Yun Efthymiou, Stephanie Manole, Andreea Wiethoff, Sarah Ye, Qiaohong Saggar, Anand McElreavey, Kenneth Krishnakumar, Shyam S. Pitt, Matthew Bello, Oscar D. Rothman, James E. Basel‐Vanagaite, Lina Hubshman, Monika Weisz Aharoni, Sharon Manzur, Adnan Y. Wirth, Brunhilde Houlden, Henry Ann Neurol Brief Communications We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1 (lew/lew) mice, observing neurophysiological features of presynaptic impairment, similar to the patients. Taken together, our findings highlight VAMP1 homozygous mutations as a cause of presynaptic CMS. Ann Neurol 2017;81:597–603 John Wiley and Sons Inc. 2017-03-29 2017-04 /pmc/articles/PMC5413866/ /pubmed/28253535 http://dx.doi.org/10.1002/ana.24905 Text en © 2017 The Authors. Annals of Neurology Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| spellingShingle | Brief Communications Salpietro, Vincenzo Lin, Weichun Vedove, Andrea Delle Storbeck, Markus Liu, Yun Efthymiou, Stephanie Manole, Andreea Wiethoff, Sarah Ye, Qiaohong Saggar, Anand McElreavey, Kenneth Krishnakumar, Shyam S. Pitt, Matthew Bello, Oscar D. Rothman, James E. Basel‐Vanagaite, Lina Hubshman, Monika Weisz Aharoni, Sharon Manzur, Adnan Y. Wirth, Brunhilde Houlden, Henry Homozygous mutations in VAMP 1 cause a presynaptic congenital myasthenic syndrome |
| title | Homozygous mutations in VAMP
1 cause a presynaptic congenital myasthenic syndrome |
| title_full | Homozygous mutations in VAMP
1 cause a presynaptic congenital myasthenic syndrome |
| title_fullStr | Homozygous mutations in VAMP
1 cause a presynaptic congenital myasthenic syndrome |
| title_full_unstemmed | Homozygous mutations in VAMP
1 cause a presynaptic congenital myasthenic syndrome |
| title_short | Homozygous mutations in VAMP
1 cause a presynaptic congenital myasthenic syndrome |
| title_sort | homozygous mutations in vamp
1 cause a presynaptic congenital myasthenic syndrome |
| topic | Brief Communications |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413866/ https://www.ncbi.nlm.nih.gov/pubmed/28253535 http://dx.doi.org/10.1002/ana.24905 |
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