The ARX problem – how an epilepsy gene escapes exome sequencing

Silence. You might wonder why you hear very little about ARX in exome studies these days. The X-chromosomal aristaless related homeobox gene was one of the first genes for epilepsies and brain malformations to be discovered. Mutations in ARX can be identified in male patients with a variety of neurodevelopmental disorders including idiopathic West Syndrome – accordingly, it’s on the differential list for patients with Infantile Spasms without a known cause. Let me tell you about the problems that the ARX gene poses for exome sequencing. Continue reading

Three things you didn’t know about epilepsy and genes

Fall colors. Just a brief summary of how this post originated. Eckernförde is a small city north of Kiel and the weekly Sunday destination of my daughter and me because of the wave pool.  This past Sunday, daylight saving and the fact that she didn’t like her dinner had confused the little girl, and we had been awake since 4AM. As a consequence, she fell asleep on the way, and I kept driving to let her sleep. We made it as far as Haddeby, and I used this time to mentally put a post together that I had been planning for some time. These are the three things that are often misunderstood with regards to epilepsy and genes. Continue reading

ST3GAL3 and exome sequencing in autosomal recessive West Syndrome

Autosomal recessive West Syndrome. Exome sequencing and other high-throughput sequencing technologies work best in the identification of recessive disorders. While many cases of West Syndrome are thought to be the result of de novo mutations, recessive inheritance is seen in a subset of patients. In a recent paper in Epilepsia, Edvardson and colleagues now report mutations in ST3GAL3 in a consanguineous Palestinian family with four affected individuals with West Syndrome. This report takes us deep into the chromosomal anatomy of the linkage region, raising the question at what point we can claim that a gene is found. Continue reading