CNV. There are different forms of genetic variation and historically, our ability to query the entire exome or genome is a relatively recent development. However, the first type of genetic variation that could be assessed in the epilepsies in large cohorts were copy number variations (CNV), small gains or losses of chromosomal materials. In a recent study, the entire Epi25 cohort was analyzed for CNVs, giving a long-needed update on the role of the structural genomic variations in various forms of epilepsies and highlighting that the overall landscape of CNVs in the epilepsies is well understood and delineated. With up to 3% of individuals with epilepsies carrying some of the recurrent CNVs, this type of genomic variation remains a rare, but important source of genetic morbidity in the epilepsies. Continue reading
Tag Archives: 16p13.11 microdeletion
Publications of the week – valproate toxicity, 15q11.2, and genetics of brain size
Issue 3/2015. This week our publications of the week are about the mechanism behind toxicity of the antiepileptic drug valproic acid in patients with POLG mutations, the phenotypic spectrum of the 15q11.2 microdeletion, and a new large-scale study on the genetics of brain size. Continue reading
The mosaic brain – single neuron copy number variations in humans
Variability. It has been rumored for quite some time, but only now is solid evidence present to show this phenomenon: the high degree of genomic diversity of human neurons. In a recent paper in Science, the genomic diversity among frontal brain neurons is explored on a cell-by-cell basis. The results are breathtaking: up to 40% of frontal cortex neurons have altered genomic material affected by large deletions or duplications. This study provides the linchpin for a plethora of new investigations aiming to understand the impact of this phenomenon in health and disease. Continue reading
Traveling beyond the ion channel
A how-to guide. July is going to be a slow month for the EuroEPINOMICS blog. Both Roland and I are going on vacation and we will use this time to migrate the entire blog to a more stable and supported server environment. While this always sounds like a quick thing to do, it involves much testing, experimenting and debating and that’s why the Channelopathist will be closed for the month of July. However, we wanted to use this time to provide our readers with brief instructions on how to navigate this blog and our past entries. Speaking of vacation, how far have you traveled beyond the ion channel? Continue reading
The 16p11.2 microdeletion: assessing the phenotypic range
The 16p11.2 story. Among the various microdeletion and microduplication syndromes located on human chromosome 16, the 16p11.2 microdeletion has unique position. Historically, this microdeletion was the first of the “neurodels” to be identified through association studies in autism, where it can be identified in 0.5% of patients. However, there is more to the phenotypes of the 16p11.2 microdeletion, which is now addressed in a recent paper assessing the full phenotypes in 72 microdeletion carriers. 16p11.2 therefore represents one of the best-investigated microdeletions to date. Continue reading
Close encounters of the third kind – rare genetic variants in families
A new beast. Rare genetic variants probably account for a significant fraction of the genetic liability to many common and rare disorders. Rare variants occupy the liability space between monogenic variants and common genetic variants. Their existence has often been postulated, and genetic investigations looking at copy number variants have elucidated some examples of rare variants. These rare variants appear to carry particular properties that are quite unexpected including the way that these variants run in families. Now, in a recent paper in the European Journal of Human Genetics, we have developed a model of the way rare variants behave in families. And there is a lot of misbehaving. Continue reading
Face to face – atypical face shape and CNVs in epilepsy
Face scan. A large high-tech camera scans your face in 3D and – using more than 30,000 data points – extracts information from your face that you were not aware of including details of your genetic make-up. What sounds like dystopic Gattaca-like science fiction at first is actually an interesting novel technique to learn more about epilepsy-related microdeletions. It seems that some of their effects might be hidden in subtle facial features that might help understand how these genetic variants contribute to disease. Continue reading
