SCN1A – This is what you need to know in 2014

Update. As information on the epilepsies caused by SCN1A mutations are amongst our most frequently read posts, we thought that a quick update on the state-of-the art regarding SCN1A would be timely. These are the ten things about SCN1A that you should known in 2014. Continue reading

The OMIM epileptic encephalopathy genes – a 2014 review

EIEE1-19. Online Mendelian Inheritance in Man (OMIM) is one of the most frequently accessed online databases for information on genetic disorders. Genes for epileptic encephalopathies are organized within a phenotypic series entitled Early Infantile Epileptic Encephalopathy (EIEE). The EIEE phenotypic series currently lists 19 genes (EIEE1-19). Let’s review the evidence for these genes as of 2014. Continue reading

Papers of the week – SCN1B, ATP1A3, NGLY1, and ontologies

Filling in. As Dennis is current fully engaged in the Helsinki meeting, I am filling in for him to present the most relevant publications in the field published in the last two weeks. This week’s publications were about functional studies, phenotype delineations, and novel gene findings. Continue reading

The return of the h-current: HCN1 mutations in atypical Dravet Syndrome

Hyperpolarization. More than a quarter of a century ago, physiologists identified an electrical current in neurons and cardiac myocytes that behaved so strangely that it was called the “queer” or “funny” current: it paradoxically caused depolarization upon hyperpolarization. This current was finally named h-current and is mediated by HCN channels. The h-current has been associated with epilepsy through functional studies, but a genetic link has been elusive so far. In a recent publication in Nature Genetics, de novo mutations in HCN1 are identified in patients with early-onset epileptic encephalopathies resembling Dravet Syndrome. Continue reading

GABRA1 and STXBP1 as novel genes for Dravet Syndrome

Beyond SCN1A. Dravet Syndrome is a severe fever-associated epileptic encephalopathy. While the large majority of patients with Dravet Syndrome carry mutations in the SCN1A gene, the genetic basis is unknown in up to 20% of patients. Some female patients with Dravet-like epilepsies have mutations in PCDH19, but other than this, no additional major gene for typical Dravet Syndrome is known. In a recent paper in Neurology, de novo mutations in GABRA1 and STXBP1 are identified as novel causes for Dravet Syndrome. In addition, several SCN1A-negative patients were shown to have mutations in SCN1A that were initially missed. Continue reading

Papers of the week – GABRA1 and STXBP1 in Dravet, gene therapy & synonymous mutations in cancers

FASTA, FASTQ, SAM, BAM, BWA, GC, GATK, IGV. Phew. Day 2 at the EuroEPINOMICS bioinformatics workshop in Leuven. Usually my work starts after the initial NGS raw data quality control and mapping procedures. Today’s topics are supposed to improve my understanding of sequencing analysis and NGS data interpretation. While we are still struggling, other scientists have done their home work already. Here are some of the remarkable publications from this week.

Leuven

Biologists, physicians and computer scientist at the EuroEPINOMICS bioinformatics workshop 2014 in Leuven

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Papers of the week – 15q11 duplications, Olig1 & Automated decision-making

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A productive week in epilepsy genetics.  Scientists and editors were certainly busy this week reporting novel variants and deletions as well the experimental and statistical advances for their interpretation.

A de novo GRIN2A missensmutation in early-onset epileptic encephalopathy. We and others have associated variants affecting the GRIN2A gene with a range of childhood focal epilepsy syndromes. Continue reading

Papers of the week – next-level mutation classifiers and 3’UTR variants in Dravet Syndrome

Bild1The future is now. This week’s publications of the week are about the next generation of in silico mutation interpretation, the power of a full genetic screen in neurodegenerative motor neuron diseases and a possible 3’UTR mutation in Dravet Syndrome. Continue reading

Papers of the week – WES Meta analysis, Dravet mice & large sequencing studies

Bild1Time flies – already thursday night again.  Here are updates on study designs to identify rare pathogenic mutations in neurodevelopment diseases, an epilepsy animal model study as well as novel statistical frameworks for large genetic screens.

The placebo effect. In a recent paper in Science Translational Medicine the group of Kam-Hansen investigated the effect of altered placebo and drug labeling changes and its outcome in patients with episodic migraine. Their results suggest that the placebo accounted for more than 50% of the drug effect.

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