التفاصيل البيبلوغرافية
| العنوان: |
Synaptotagmin 2 Mutations Cause an Autosomal-Dominant Form of Lambert-Eaton Myasthenic Syndrome and Nonprogressive Motor Neuropathy. |
| المؤلفون: |
Herrmann, David N.1, Horvath, Rita2, Sowden, Janet E.1, Gonzales, Michael3, Sanchez-Mejias, Avencia3, Guan, Zhuo4, Whittaker, Roger G.5, Almodovar, Jorge L.6, Lane, Maria2, Bansagi, Boglarka2, Pyle, Angela2, Boczonadi, Veronika2, Lochmüller, Hanns2, Griffin, Helen2, Chinnery, Patrick F.2, Lloyd, Thomas E.7, Littleton, J. Troy4, Zuchner, Stephan3 szuchner@med.miami.edu |
| المصدر: |
American Journal of Human Genetics. Sep2014, Vol. 95 Issue 3, p332-339. 8p. |
| مصطلحات موضوعية: |
*SYNAPTOTAGMINS, *LAMBERT-Eaton myasthenic syndrome, *NEUROPATHY, *CALCIUM-binding proteins, *GENETIC code, *NEURONS |
| مستخلص: |
Synaptotagmin 2 is a synaptic vesicle protein that functions as a calcium sensor for neurotransmission but has not been previously associated with human disease. Via whole-exome sequencing, we identified heterozygous missense mutations in the C2B calcium-binding domain of the gene encoding Synaptotagmin 2 in two multigenerational families presenting with peripheral motor neuron syndromes. An essential calcium-binding aspartate residue, Asp307Ala, was disrupted by a c.920A>C change in one family that presented with an autosomal-dominant presynaptic neuromuscular junction disorder resembling Lambert-Eaton myasthenic syndrome. A c.923C>T variant affecting an adjacent residue (p.Pro308Leu) produced a presynaptic neuromuscular junction defect and a dominant hereditary motor neuropathy in a second family. Characterization of the mutation homologous to the human c.920A>C variant in Drosophila Synaptotagmin revealed a dominant disruption of synaptic vesicle exocytosis using this transgenic model. These findings indicate that Synaptotagmin 2 regulates neurotransmitter release at human peripheral motor nerve terminals. In addition, mutations in the Synaptotagmin 2 C2B domain represent an important cause of presynaptic congenital myasthenic syndromes and link them with hereditary motor axonopathies. [ABSTRACT FROM AUTHOR] |
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