Clinical Trial Summary
Rare diseases (affecting less than one in 2,000 people) are a major public health issue.
There are about 8,000 rare diseases and they affect more than 3 million people in France.
Most of these diseases are diagnosed in children, and they are responsible for 10% of deaths
before the age of 5. Up to 80% of these diseases are believed to be of genetic origin. New
generation high throughput sequencing (HTS) technologies, which allow the study of an
individual's entire genome, have emerged in recent years as a tool of choice for the study of
rare diseases. Our team was the first in France to demonstrate the value of exome sequencing
(ES: all coding regions (exons), representing 1% of the total genome size) in the diagnosis
of severe diseases in pediatric patients, developmental anomalies and intellectual
disability.
Although it represents a significant advance in the diagnosis of genetic diseases, ES
provides a contributing result in only about 30% of cases in patients with no obvious
clinical diagnosis and with normal CGH-array. Sequencing the entire genome (GS) promises to
improve the ability to study the causes of genetic diseases, with an expected diagnostic rate
of 50 to 60% through the concomitant identification of point variations, CNVs and structural
variations. While some international teams have already implemented GS in the diagnosis of
rare diseases, only two teams report the use of trio GS in emergency situations in the
neonatal period, with a low yield for first-line diagnostic use (31 and 42% respectively). It
is therefore essential that these preliminary results be compared with other studies before
considering the deployment of GS in diagnostic, early detection or rapidly evolving emergency
situations, such as neonatal resuscitation or pediatric neurological distress.
