An Exploratory Study Using Electronic Medical Records to Assess the Feasibility of Establishing Cohorts of Patients with Genetic Causes of Parkinson's Disease.

Background: More efficient screening methods are needed to improve the ability to identify and follow genetic cohorts in Parkinson's disease (PD).

Objective: To explore the use of the electronic medical records (EMRs) to identify participants with PD.

Methods: Using an algorithm previously developed in collaboration with Maccabi Healthcare Services (MHS), approximately 5,200 participants with PD were identified, more than 3,200 were screened, and 837 participants were enrolled and genotyped for leucine-rich repeat kinase 2 (LRRK2) and beta-glucocerebrosidase (GBA) variants.

A calcium channel mutant mouse model of hypokalemic periodic paralysis.

Hypokalemic periodic paralysis (HypoPP) is a familial skeletal muscle disorder that presents with recurrent episodes of severe weakness lasting hours to days associated with reduced serum potassium (K+). HypoPP is genetically heterogeneous, with missense mutations of a calcium channel (Ca(V)1.1) or a sodium channel (Na(V)1.

A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis.

Hypokalemic periodic paralysis (HypoPP) is an ion channelopathy of skeletal muscle characterized by attacks of muscle weakness associated with low serum K+. HypoPP results from a transient failure of muscle fiber excitability. Mutations in the genes encoding a calcium channel (CaV1.

Gating pore currents in DIIS4 mutations of NaV1.4 associated with periodic paralysis: saturation of ion flux and implications for disease pathogenesis.

S4 voltage-sensor mutations in CaV1.1 and NaV1.4 channels cause the human muscle disorder hypokalemic periodic paralysis (HypoPP).

Paradoxical depolarization of BA2+- treated muscle exposed to low extracellular K+: insights into resting potential abnormalities in hypokalemic paralysis.

The combination of sarcolemmal depolarization and hypokalemia exhibited by the different forms of hypokalemic paralysis has been attributed to abnormalities of the K+ conductance governing the resting membrane potential (V(REST)). Supportive data have been observed in muscle fibers biopsied from patients with familial hypokalemic periodic paralysis (HypoPP) that paradoxically depolarize at low K+. Although this observation is consistent with anomalous K+ conductance, rigorous experimental support is lacking.

A Na+ channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore.

The heritable muscle disorder hypokalemic periodic paralysis (HypoPP) is characterized by attacks of flaccid weakness, brought on by sustained sarcolemmal depolarization. HypoPP is genetically linked to missense mutations at charged residues in the S4 voltage-sensing segments of either CaV1.1 (the skeletal muscle L-type Ca(2+) channel) or NaV1.

Slow inactivation does not block the aqueous accessibility to the outer pore of voltage-gated Na channels.

Slow inactivation of voltage-gated Na channels is kinetically and structurally distinct from fast inactivation. Whereas structures that participate in fast inactivation are well described and include the cytoplasmic III-IV linker, the nature and location of the slow inactivation gating mechanism remains poorly understood. Several lines of evidence suggest that the pore regions (P-regions) are important contributors to slow inactivation gating.