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Fig. 1 | Molecular Brain

Fig. 1

From: Rare functional missense variants in CACNA1H: What can we learn from Writer’s cramp?

Fig. 1

Segregation analysis and structural and functional characterization of two putative damaging missense variants in CACNA1H. a, b Pedigrees of the Dutch families with the c.1441C > T p.Arg481Cys variation in CACNA1H and the c.5641G > A p.Glu1881Lys variation, respectively. Open symbols indicate unaffected family members. Black symbols indicate affected members. Individuals marked with an asterisk were clinically examined and DNA was available for genetic testing. The index patient is marked by an arrow. c Arginine and cysteine at position 481 in the predicted structural model of Cav3.2. The introduction of a cysteine at position 418 might lead to destabilization of the bundle of α-helices (in green). d Glutamic acid at position 1881 is predicted to interact with adjacent arginines located at positions 1596 and 1597. e Average current densities (pA/pF) as a function of voltage in tsA-201 cells transfected with wild type (WT) Cav3.2, R481C and E1881K-mutant Cav3.2 channels. f Bar graph represents the corresponding maximum slope conductance Gmax. Values are represented as mean ± SEM. Solid lines are fits with the Boltzmann equation. g Mean normalized voltage dependence of steady-state inactivation of WT, R481C and E1881K channels. h Mean half-inactivation potentials determined via the Boltzmann equation from fits to individual steady-state inactivation curves. Asterisks denote statistical significance relative to wild type (**p = 0.0053, Student’s t-test). i Time course of recovery from inactivation. j Time constant of recovery from inactivation determined via individual fits of the recovery from inactivation curves. Asterisks denote statistical significance relative to WT Cav3.2 (*p = 0.0275, ****p < 0.0001, Student’s t-test)

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