| Autor: |
BINDA, ANNA, RIVOLTA, ILARIA, Cardani, R, Renna, LV, Fossati, B, Bosè, F, Botta, A, Valaperta, R, Meola, G |
| Přispěvatelé: |
Binda, A, Cardani, R, Renna, L, Fossati, B, Bosè, F, Botta, A, Valaperta, R, Meola, G, Rivolta, I |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Popis: |
Myotonia, mild and inconsistent in DM2, has been correlated with the disruption of the alternative splicing of CLCN1. Mutations in CLCN1 and SCN4A genes can act as modifiers in these patients leading to an amplification of their myotonic symptoms. A DM2 patient with an early severe myotonia came to our attention. No mutation was found on CLCN1 gene, but SCN4A gene showed G2717C base exchange, a variant considered a benign polymorphism. In the proband mother, also affected by DM2 but without the SCN4A polymorphism, no clinical myotonia was observed. The aim of the study was to compare the sodium current properties in myoblasts and the action potential features in myotubes derived from the proband and his mother muscle biopsies. Patch clamp was used for electrophysiological recordings. Preliminary results in myoblasts showed no change in the steady state activation properties but a significant shift in its availability curve (V1/2 -74±0,2 mV n=8 and V1/2 -79±0,2 mV n=9 proband and mother respectively); in myotubes, the minimum current necessary to elicit an action potential was lower in the proband than in his mother (272±6 pA n=9 and 462±130 pA, n=6), respectively. In conclusion we suggest that: SCN4A polymorphism may induce a more excitable substrate potentially aggravating the effect of the DM2 mutations; that SCN4A gene screening should be performed in DM2 patients with early and severe myotonia without mutations in CLCN1 gene, and finally that the detection of modifying factors may have important clinical implication such as the identification of appropriate drug treatment |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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