EFHC1 variants are the most common mutations in inherited myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions of juvenile myoclonic epilepsy (JME). We reanalyzed 54 EFHC1 variants associated with epilepsy from 17 cohorts based on National Human Genome Research Institute (NHGRI) and American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants.
We calculated Bayesian LOD scores for variants in coinheritance, unconditional exact tests and odds ratios (OR) in case-control associations, allele frequencies in genome databases, and predictions for conservation/pathogenicity. We reviewed whether variants damage EFHC1 functions, whether efhc1-/- KO mice recapitulate CTC convulsions and \"microdysgenesis\" neuropathology, and whether supernumerary synaptic and dendritic phenotypes can be rescued in the fly model when EFHC1 is overexpressed. We rated strengths of evidence and applied ACMG combinatorial criteria for classifying variants.
Nine variants were classified as \"pathogenic,\" 14 as \"likely pathogenic,\" 9 as \"benign,\" and 2 as \"likely benign.\" Twenty variants of unknown significance had an insufficient number of ancestry-matched controls, but ORs exceeded 5 when compared with racial/ethnic-matched Exome Aggregation Consortium (ExAC) controls.
NHGRI gene-level evidence and variant-level evidence establish EFHC1 as the first non-ion channel microtubule-associated protein whose mutations disturb R-type VDCC and TRPM2 calcium currents in overgrown synapses and dendrites within abnormally migrated dislocated neurons, thus explaining CTC convulsions and \"microdysgenesis\" neuropathology of JME.Genet Med 19 2, 144-156.

Standards for human exposure to electromagnetic fields typically express maximum permissible exposure limits as a function of frequency. Often, these limits have been derived from experiments or theoretical models involving sinusoidal waveforms. In many practical situations, however, the relevant waveforms of interest may not be sinusoidal, such as with waveforms having harmonic distortion, or with pulsed waveforms. This paper evaluates methods for applying sinusoidal exposure standards to non-sinusoidal waveforms in the frequency regime below a few MHz where electrostimulation is the dominant mechanism. Waveforms treated include those of a pulsed or mixed frequency variety. We evaluate acceptance criteria for mixed frequency exposure using summation formulae cited by IEEE C95.1, ICNIRP, and NRPB. This is carried out using a Fourier synthesis of various waveshapes. Also evaluated is an acceptance criterion based on the peak of the exposure waveform. Excitation thresholds are evaluated using a myelinated nerve model that accounts for the nonlinear electrodynamics of the neural membrane. It is shown that a method based on the peak and phase duration of the in situ field waveform provides a typically conservative test for compliance with non sinusoidal waveforms. An alternate method, based on amplitude summation of the Fourier components of the applied waveforms, can also provide a meaningful test, albeit a more conservative one.

The testing of nerve conduction using electromyography (EMG) is a frequently used diagnostic method for the identification of various neuropathies. The present article illustrates a variety of conditions on the basis of clinical data, and suggests how one can obtain the best results by observing a few simple rules.