Unsolved cases. We are in an era of dramatic progress in understanding the genetic causes of neurologic disorders. In spite of this progress, many cases remain unsolved even after whole exome sequencing. One hypothesis for this missing heritability is that “non-coding” mutations outside the exome may explain at least some of these unsolved cases. A recent study looked at de novonon-coding variants in patients with neurodevelopmental disorders. The study sheds new light on this question and reminds us that, despite all the recent progress, there is much still to learn about vast portions of the genome. Continue reading
Author Archives: Colin Ellis
The power of 3 – exome trios in neurodevelopmental disorders with epilepsy
Trio exomes. The concept of neurodevelopmental disorders is an umbrella term including intellectual disability, developmental delay, and autism spectrum disorder. About one quarter of these patients have epilepsy, including epileptic encephalopathy, in which the epileptic activity itself contributes to developmental delay or regression. One major cause of these disorders are de novomutations, which are present in the child but not present in either of the parents. A recent publication in Nature Genetics looked for de novo variants in nearly 6,700 patients with neurodevelopmental disorders, nearly 2,000 of whom had epilepsy. This study is an order of magnitude larger than the largest previous study of this kind and represents an important effort in epilepsy genetics. Here is what we want to review their major findings. Continue reading
