Can’t you hear the radio? This is what you need to know about LGI1 in 2015

Auditory. The next gene in our weekly review is LGI1. We chose LGI1 for mainly two reasons. First, it is not a gene for epileptic encephalopathies, but for familial focal epilepsies and we are currently working up a large family with an LGI1 mutation. While the conditions of the mTOR pathways were discussed quite frequently, LGI1 was a little left behind. Secondly, there were various updates on LGI1 that didn’t really warrant a full post. Therefore, we have collected this in a summary post. Continue reading

Publications of the week: genes for Alzheimer’s disease, essential tremor, and ACC

Issue 9/2015. This issue of the publications of the week is about novel genetic findings for neurological disorders that we usually don’t discuss on our blog. Given that there were several reports this week, I thought that thinking a bit outside the box would be a good theme for this week. Follow us on a brief journey of novel genes for Alzheimer’s disease, essential tremor, and agenesis of corpus callosum.

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Here are 5 quick free web-based tools for gene interpretation

Exome rounds. Interpreting genetic variants is one of the main challenges in genomic medicine. Many people have perceived barriers to starting some of the variant analysis themselves, given that there is the widespread notion that this requires expert bioinformatics knowledge. However, this is somewhat a concept of the past. There are some beautiful and simple tools online that you can use for free. Here are my favorite web-based tools for variant interpretation. Continue reading

Here is why CADD has become the preferred variant annotation tool

Variant annotation. In both clinical practice and within existing research projects, we’re often faced with the issue of telling whether a given variant is benign or whether it is pathogenic. In silico prediction tools are designed to help this decision making process. However, there are so many of them and it is often hard to assess which tool works best. In a 2014 publication in Nature Genetics, the CADD score was introduced as comprehensive tool that aims to take the results of many known prediction tools into account. Follow me on a journey that takes us on hyperplanes, support vector machines and every possible variant in the human genome. Continue reading

Mysteries of a neuronal pathfinder – this is what you should know about PCDH19 in 2015

Protocadherin. There are some genes that we have mentioned less frequently on our blog than we should have. PCDH19 and CDKL5 are two examples of this. With this post, we try to catch up by reviewing some of the new findings related to PCDH19 Female Epilepsy including the role of neurosteroids, anti-NMDA receptor antibodies, stiripentol and the mechanism behind this epilepsy. Continue reading

Publications of the week: CDKL5, KIF1A, and familial cortical tremor

Issue 7/2015. I am realizing that we are a little behind with our weekly paper review and I hope that we can use the month of July to catch up. Our publications of the week include functional studies on CDKL5 targets that may suggest future therapy development, the recessive/de novo paradox of KIF1A and an attempt to understand the genetics of familial cortical tremor. Continue reading

Robinsoe Crusoe, NFXL1, and speech delay

Founder variant. Specific language impairment (SLI) is a common neurodevelopmental disorder, presenting as delays in acquiring language skills in children who have no hearing loss or other developmental delays. There is a strong genetic component, but the genetic architecture of SLI is entirely unknown. In a recent publication in PLOS Genetics, exome sequencing is performed in the founder population of the Robinson Crusoe Island where SLI is common. Using a combination of exome sequencing and association study, the autors identify a variant In NFXL1 as a plausible candidate for language delay. Continue reading