NDD. Trio-exome sequencing is the gold standard to identify the underlying genetic basis in individuals with neurodevelopmental disorders. De novo variants account for the vast majority of causative genetic findings once a diagnosis is made, but the overall genetic landscape is very heterogeneous, with few genes explaining more than 1% of the genetic morbidity. As the largest study of its kind to date, a recent publication in Nature assessed the spectrum of de novo variants in neurodevelopmental disorders in more than 31,000 individuals. The authors identify more than 250 disease-associated genes, highlight 28 novel genetic etiologies, and highlight signals in their data that hint at more than 1,000 disease-associated genes yet to be discovered. In this blog post, I have summarized the five take-home messages from this large study. Continue reading
Tag Archives: diagnostic exome sequencing
Discrepancies in interpretation – when can exomes speak from themselves?
Interpretation. There is huge promise in discovering the genetic basis of neurodevelopmental disorders using exome sequencing, but it is often not clear how ambiguous results are communicated to families. In a recent publication in Clinical Genetics, the authors try to understand what happens to exome results as they land on the clinician’s desk – and leave us with the conclusion that diagnostic exome sequencing when reviewed in a clinical setting may have a false positive rate of up to 20% with 5% of false negatives. Continue reading
Why you need to know what EGI stands for
Epilepsy Genetics Initiative – A Signature Program of CURE from CUREepilepsy on Vimeo.
The Epilepsy Genetics Initiative. If you had told me last week that the next era of epilepsy genetics would be announced by an animated cartoon, I wouldn’t have believed you. Earlier this week, the Epilepsy Genetics Initiative (EGI) was launched, an emerging large exome repository that will help us connect dots in epilepsy genetics research by centralizing genetic data for research. These are the three things that I have learned from the EGI launch. Continue reading
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
