D-galactose Supplementation for the Treatment of Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE): A Pilot Trial of Precision Medicine After Epilepsy Surgery.

MOGHE is defined as mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Approximately half of the patients with histopathologically confirmed MOGHE carry a brain somatic variant in the SLC35A2 gene encoding a UDP-galactose transporter. Previous research showed that D-galactose supplementation results in clinical improvement in patients with a congenital disorder of glycosylation due to germline variants in SLC35A2.

Atlantic herring () population structure in the Northeast Atlantic Ocean.

The Atlantic herring L has a vast geographical distribution and a complex population structure with a few very large migratory units and many small local populations. Each population has its own spawning ground and/or time, thereby maintaining their genetic integrity. Several herring populations migrate between common feeding grounds and over-wintering areas resulting in frequent mixing of populations.

Not Just Loss-of-Function Variations: Identification of a Hypermorphic Variant in a Patient With a CDKL5 Missense Substitution.

Background And Objectives: CDKL5 deficiency disorder (CDD) is a neurodevelopmental encephalopathy characterized by early-onset epilepsy and impaired psychomotor development. Variations in the X-linked gene coding for a kinase cause CDD. Molecular genetics has proved that almost all pathogenic missense substitutions localize in the N-terminal catalytic domain, therefore underlining the importance for brain development and functioning of the kinase activity.

Identification of male heterogametic sex-determining regions on the Atlantic herring Clupea harengus genome.

The sex determination system of Atlantic herring Clupea harengus L., a commercially important fish, was investigated. Low coverage whole-genome sequencing of 48 females and 55 males and a genome-wide association study revealed two regions on chromosomes 8 and 21 associated with sex.

Using long and linked reads to improve an Atlantic herring (Clupea harengus) genome assembly.

Atlantic herring (Clupea harengus) is one of the most abundant fish species in the world. It is an important economical and nutritional resource, as well as a crucial part of the North Atlantic ecosystem. In 2016, a draft herring genome assembly was published.

Parental mosaicism in epilepsies due to alleged de novo variants.

Severe early onset epilepsies are often caused by de novo pathogenic variants. Few studies have reported the frequency of somatic mosaicism in parents of children with severe epileptic encephalopathies. Here we aim to investigate the frequency of mosaicism in the parents of children with epilepsy caused by alleged de novo variants.

Mesial Temporal Sclerosis in SCN1A-Related Epilepsy: Two Long-Term EEG Case Studies.

Patients with temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (MTS) are eligible candidates for resective epilepsy surgery. We report on 2 male patients aged 4 years with suspected TLE due to MTS who were referred for presurgical evaluation. Both patients came to medical attention within the first year of life suffering from febrile status epileptici and subsequent unprovoked seizures.

Incorporating epilepsy genetics into clinical practice: a 360°evaluation.

We evaluated a new epilepsy genetic diagnostic and counseling service covering a UK population of 3.5 million. We calculated diagnostic yield, estimated clinical impact, and surveyed referring clinicians and families.

Mutations in GABRB3: From febrile seizures to epileptic encephalopathies.

Objective: To examine the role of mutations in GABRB3 encoding the β subunit of the GABA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes.

Methods: We performed massive parallel sequencing of GABRB3 in 416 patients with a range of epileptic encephalopathies and childhood-onset epilepsies and recruited additional patients with epilepsy with GABRB3 mutations from other research and diagnostic programs.

Results: We identified 22 patients with heterozygous mutations in GABRB3, including 3 probands from multiplex families.

Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies.

In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in a patient can still be difficult, since extensive phenotypic and genetic heterogeneity has been observed in many monogenic epilepsies. This study aimed to analyze the genetic basis of a wide spectrum of epilepsies with age of onset spanning from the neonatal period to adulthood.

Association between genes on chromosome 19p13.2 and panic disorder.

Panic disorder (PD) is a severe and disabling mental disorder, which is moderately heritable. In a previous study, we carried out a genome-wide association study using patients with PD and control individuals from the isolated population of the Faroe Islands and identified chromosome 19p13.2 as a candidate region.

Phenotypic spectrum of GABRA1: From generalized epilepsies to severe epileptic encephalopathies.

Objective: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations.

Methods: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected.

Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation.

Objective: Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination-known as infantile convulsions and paroxysmal choreoathetosis (ICCA)-are related autosomal dominant diseases. PRRT2 (proline-rich transmembrane protein 2 gene) has been identified as the major gene in all 3 conditions, found to be mutated in 80 to 90% of familial and 30 to 35% of sporadic cases.

Methods: We searched for the genetic defect in PRRT2-negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed cliniconeurophysiological workup.

The contribution of next generation sequencing to epilepsy genetics.

During the last decade, next generation sequencing technologies such as targeted gene panels, whole exome sequencing and whole genome sequencing have led to an explosion of gene identifications in monogenic epilepsies including both familial epilepsies and severe epilepsies, often referred to as epileptic encephalopathies. The increased knowledge about causative genetic variants has had a major impact on diagnosis of genetic epilepsies and has already been translated into treatment recommendations for a few genes. This article provides an overview of how next generation sequencing has advanced our understanding of epilepsy genetics and discusses some of the recently discovered genes in monogenic epilepsies.

Mutations in KCNT1 cause a spectrum of focal epilepsies.

Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy (SUDEP), in addition to patients with NFLE and MMFSI.

Clinical Phenotype of De Novo Mutation: Case Report and Review of Literature.

Mutations in the guanine nucleotide-binding protein (G protein), α activating activity polypeptide O () gene have recently been described in 6 patients with early infantile epileptic encephalopathies. In the present study, we report the phenotype and the clinical course of a 4-year-old female with an epileptic encephalopathy (Ohtahara syndrome) and profound intellectual disability due to a de novo mutation (c.692A>G; p.

Primary functions of the quadratus femoris and obturator externus muscles indicated from lengths and moment arms measured in mobilized cadavers.

Background: The small muscles of the pelvis and hip are often implicated in painful conditions. Although the quadratus femoris and obturator externus are usually described as external rotators of the hip, little is known about how they change their lengths and moment arms during human movement. Therefore, more precise measurements defining the positions and directions for their maximal strength and stretch are needed to better describe their functions and guide the clinical approach to pain.

Lengths of the external hip rotators in mobilized cadavers indicate the quadriceps coxa as a primary abductor and extensor of the flexed hip.

Background: The primary function of the external rotators of the hip is inadequately described. The descriptions for peak strength and stretch take no account of how these muscles change their length during normal movement. The latter relationship is known to greatly influence contraction forces and reflect moment arms.

Are TMEM genes potential candidate genes for panic disorder?

We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12, a previously reported candidate region for PD.

The role of SLC2A1 in early onset and childhood absence epilepsies.

Early Onset Absence Epilepsy constitutes an Idiopathic Generalized Epilepsy with absences starting before the age of four years. Mutations in SLC2A1, encoding the glucose transporter, account for approximately 10% of EOAE cases. The role of SLC2A1 mutations in absence epilepsies with a later onset has not been assessed.

A genome-wide study of panic disorder suggests the amiloride-sensitive cation channel 1 as a candidate gene.

Panic disorder (PD) is a mental disorder with recurrent panic attacks that occur spontaneously and are not associated to any particular object or situation. There is no consensus on what causes PD. However, it is recognized that PD is influenced by environmental factors, as well as genetic factors.

Effect of training with different mechanical loadings on MyHC and GLUT4 changes.

Purpose: There is an inverse relationship between insulin sensitivity and percentage of myosin heavy chain IIx (MyHC IIx) isoform in sedentary, obese, and type 2 diabetic humans. How different exercise conditions may reduce the proportion of MyHC IIx and in parallel elevate glucose transporter 4 (GLUT4) content is interesting in a therapeutic setting. This study investigates the nature of exercise signals regulating MyHC gene switching and whether it is accompanied by GLUT4 changes.

Effect of training with different intensities and volumes on muscle fibre enzyme activity and cross sectional area in the m. triceps brachii.

This study primarily examined how intermittent versus continuous endurance training, using similar or dissimilar volumes, affected muscle fibre enzyme activities in the triceps brachii muscle. Thirty-two subjects performed either intermittent (60% of 1RM) or continuous (30% of 1RM) elbow extensions 3 times week(-1) in a training apparatus. Training was performed until either a low (five) or a high volume (8 weeks) was accumulated.

Effect of training and detraining on the expression of heat shock proteins in m. triceps brachii of untrained males and females.

Forty untrained persons were randomized to four different training protocols that exercised the m. triceps brachii. Group 1 and 2 performed high intensity (HI) elbow extensions and group 3 and 4 performed low intensity (LI) elbow extensions.