The Dutch researchers were entering new territory and so needed to write the rulebook themselves. "There were no best practice guidelines available for exome sequencing, and so we had to create diagnostic workflows, procedures and criteria. What criteria did we have to set before we could authorise the outcome? What type of informed consent was necessary? How could we organise confirmation of our results? All these questions had to be answered, and we undertook numerous discussions with clinical geneticists, researchers and ethicists before we could get started", Dr. Nelen says.
The results then needed to be confirmed. "We validated our results by using Sanger sequencing, the standard method of genetic diagnosis which has a very high sensitivity and specificity", Dr. Nelen will say. In addition to ID and blindness, confirmed diagnostic results in the other diseases analysed to date were impressive. In deafness disease-causing mutations were found in about 20% of cases, in movement disorders between 15 20%, and in OXPHOS diseases causal mutations were found in about 25% of the patients studied.
"Although it is often not possible to treat their diseases, we should take into account that most of these patients will have had a long and worrying journey through different doctors and hospitals before they are diagnosed", says Dr. Nelen. "Exome sequencing can shorten that route, and it can also simplify the work of clinicians because they don't have to make a decision about which gene to test for with 100 or more genes per disease, that can be a very difficult decision to make. Exome sequencing tests for all the causative gene mutations at the same time, and that means tha
|Contact: Mary Rice|
European Society of Human Genetics