Half Moon Bay. I am on my way back from the Precision Medicine Workshop at Half Moon Bay, realizing again that blog posts from scientific meetings are often boring and difficult to write. However, let me try to put together a few thoughts about this meeting. Basically, there are three challenges for epilepsy genetics in the era of precision medicine. Continue reading
Tag Archives: recessive mutations
WWOX, spinocerebellar ataxia, neurodegeneration, and epilepsy
Exomes. Massive parallel sequencing technologies are ideally suited to identify the genetic basis of monogenic disorders, particularly recessive diseases. In a recent publication in the Orphanet Journal of Rare Disease, Abdel-Salam and collaborators identify a homozygous mutation in WWOX in a family with epileptic encephalopathy and neurodegeneration. Their study highlights the issues of how to interpret recessive gene findings spanning different phenotypes identified in the era of exome sequencing. 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
One in four – the carrier rate of recessive diseases
How frequent? With all the genetic information around, we are often wondering how much genetic morbidity is really hidden in our genomes. Yes, everybody is a knock-out for 1-3 genes, but in most cases, these variants do not cause disease. However, what happens if you apply genomics to estimate the burden of known disease variants? Now in a recent paper in Genetics in Medicine by Lazarin and colleagues, the carrier frequency for ~400 variants known to cause ~100 recessive disorders is investigated. 24% of all individuals are carriers for at least one recessive disorder. Continue reading
Recessive mutations in autism – the return of hidden metabolic disorders
My wrong guesses of 2012. Two weeks ago during a presentation, I had to admit that there is little evidence for a large contribution of recessive or compound heterozygous mutations in epileptic encephalopathies. At the beginning of 2012, I had initially suggested that recessive or compound heterozygous mutation of known neurometabolic disorders could be identified through exome sequencing in sporadic epileptic encephalopathies. However, as of 2013, there is little evidence for this in our data or the data from other consortia. Now, two papers in Cell suggest a significant contribution of recessive mutations in autism including a revival of the “hidden neurometabolic hypothesis”. Continue reading
