Helle Hjalgrim
A5091808177- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Metabolism and Genetic Disorders
- Autism Spectrum Disorder Research
- Obsessive-Compulsive Spectrum Disorders
- Congenital heart defects research
- Pharmacological Effects and Toxicity Studies
- Glycogen Storage Diseases and Myoclonus
- Cellular transport and secretion
- EEG and Brain-Computer Interfaces
- Diet and metabolism studies
- RNA regulation and disease
- Neurological disorders and treatments
- Amino Acid Enzymes and Metabolism
- RNA modifications and cancer
- Hemoglobinopathies and Related Disorders
- RNA and protein synthesis mechanisms
- Prenatal Screening and Diagnostics
- Cardiac electrophysiology and arrhythmias
- Cleft Lip and Palate Research
- Neonatal and fetal brain pathology
- Ion Transport and Channel Regulation
- Chromosomal and Genetic Variations
Statens Serum Institut
2006-2021
Rigshospitalet
2021
Copenhagen University Hospital
2016-2021
University of Southern Denmark
2011-2020
Filadelfia
2009-2020
University of Copenhagen
1999-2020
Odense University Hospital
2020
Danish Gas Technology Centre (Denmark)
2013-2019
DNA Diagnostic (Denmark)
2016-2018
Brigham and Women's Hospital
2018
Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with spectrum of epilepsies and neurodevelopmental disorders. Here, we report phenotypes 71 patients review 130 previously reported patients. We found that (i) encephalopathies infantile/childhood onset (≥3 months age) occur almost as often those an early infantile (<3 months), are thus more frequent than reported; (ii) distinct can be seen within late group, including myoclonic-atonic epilepsy...
Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the factors predisposing to idiopathic remain elusive. Studies structural genomic variations have revealed significant excess recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability schizophrenia. Microdeletions 15q13.3 recently been shown constitute strong risk factor common...
The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report genome-wide mega-analysis involving 15,212 individuals with epilepsy 29,677 controls, which reveals 16 significant loci, of 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely genes at these majority in genetic generalized epilepsies. These diverse biological functions, including coding for ion-channel subunits, transcription factors...
SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). mutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate phenotype mutations.We used high-throughput sequence analysis of gene in 683 patients a range epileptic encephalopathies. In addition, we ascertained cases from other centers. A detailed clinical history was obtained together review EEG imaging data.Seventeen de novo heterozygous were studied. Seizure onset occurred...
De novo mutations in SYNGAP1, which codes for a RAS/RAP GTP-activating protein, cause nonsyndromic intellectual disability (NSID). All disease-causing point identified until now SYNGAP1 are truncating, raising the possibility of an association between this type and NSID. Here, we report identification first pathogenic missense (c.1084T>C [p.W362R], c.1685C>T [p.P562L]) three novel truncating (c.283dupC [p.H95PfsX5], c.2212_2213del [p.S738X], (c.2184del [p.N729TfsX31]) patients with A subset...
To determine the genes underlying Dravet syndrome in patients who do not have an SCN1A mutation on routine testing.We performed whole-exome sequencing 13 SCN1A-negative with and targeted resequencing 67 additional to identify new for this disorder.We detected disease-causing mutations 2 novel syndrome, GABRA1 4 cases STXBP1 3. Furthermore, we identified 3 previously undetected mutations, suggesting that occur even more than currently accepted ∼ 75% of cases.We show make a significant...
To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand phenotypic spectrum encephalopathy.Eighty-four unexplained NEE were screened for using classic Sanger sequencing. Clinical data 6 additional detected by gene panel collected. Detailed phenotyping was performed particular attention seizure frequency, cognitive outcome, video-EEG.In cohort, we identified 9 different heterozygous de novo missense 11 84 (13%). Two recurrent...
Summary Our objective was to assess the clinical reliability of a wrist‐worn, wireless accelerometer sensor for detecting generalized tonic–clonic seizures ( GTCS ). Seventy‐three consecutive patients (age 6–68 years; median 37 years) at risk having and who were admitted long‐term video–electroencephalography EEG ) monitoring unit LTM recruited in three centers. The reference standard considered seizure time points identified by experienced neurophysiologists, based on video‐ recordings...
Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination-known as convulsions choreoathetosis (ICCA)-are related autosomal dominant diseases. PRRT2 (proline-rich transmembrane protein 2 gene) has been identified the major gene in all 3 conditions, found to be mutated 80 90% of 30 35% sporadic cases.We searched for genetic defect PRRT2-negative, unrelated families with BFIS or ICCA using whole exome targeted panel sequencing, performed a...
To determine the phenotypic spectrum caused by mutations in GRIN1 encoding NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology.We collected molecular clinical data from several diagnostic research cohorts. Functional consequences of were investigated Xenopus laevis oocytes.We identified heterozygous de novo 14 individuals reviewed phenotypes all 9 previously reported patients. These 23 presented with a distinct phenotype profound developmental delay,...
Mutations in FOXL2, a forkhead transcription factor gene, have recently been shown to cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, rare genetic disorder. In BPES type complex eyelid malformation is associated with premature ovarian failure (POF), whereas II the defect occurs as an isolated entity. this study, we describe identification of novel mutations FOXL2 gene families, sporadic patients, families where could not be established. 67% patients studied,...
Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% all epilepsies. Despite their high heritability 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out two-stage genome-wide association study (GWAS) including 3020 patients with 3954 controls European ancestry. dissect syndrome-related variants, also explored two distinct subgroups comprising 1434...
Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. abnormalities are common brain malformations a wide clinical spectrum ranging from severe disability to normal cognitive function. The etiology is expected be genetic as much 30-50% the cases, but underlying cause remains unknown majority cases. By next-generation mate-pair sequencing we mapped chromosomal breakpoints patient de novo balanced translocation,...
To delineate phenotypic heterogeneity, we describe the clinical features of a cohort patients with GABRA1 gene mutations.Patients mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data collected. Functional analysis 4 selected was performed using Xenopus laevis oocyte expression system.The study included 16 novel probands 3 additional family members disease-causing mutation in gene. The spectrum varied from unspecified epilepsy (1), juvenile...
In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in patient can still be difficult, since extensive phenotypic and heterogeneity has observed many monogenic epilepsies. This study aimed to analyze the basis of wide spectrum epilepsies age onset spanning from neonatal period adulthood. A gene panel targeting 46 epilepsy was used on cohort 216 patients consecutively referred for testing. The had range different benign seizures...
Dravet syndrome is a severe infantile-onset epileptic encephalopathy associated with mutations in the sodium channel alpha-1 subunit gene SCN1A. We aimed to describe incidence of Danish population. Based on 6-year birth cohort from 2004 2009, we propose an 1:22,000, which higher than what has been established earlier. identified 17 cases SCN1A mutation-positive syndrome. Fifteen patients were found, by conventional Sanger sequencing. Two additional clinical syndrome, but without detectable...
Summary The electroencephalography ( EEG ) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis recordings. interobserver agreement in interpretation only moderate. This partly due to method reporting findings free‐text format. purpose our endeavor was create computer‐based system for assessment reporting, where physicians would construct reports choosing from predefined elements each feature, as well clinical phenomena (for...
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% all epilepsies. Genomic copy number variations (CNVs) constitute important risk factors GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence 200 markers) were assessed by Affymetrix SNP 6.0 array in European case-control cohorts 1,366 patients 5,234 ancestry-matched controls. We aimed to: 1) assess...