Study of the Diagnostic Value of "Rapid" High Throughput Genome Sequencing Analysis in Diagnostic Emergency Situations

NCT03956069 | Completed

• 1 other identifier: SORLIN PHRCI 2018
• Study Type: observational
• Target: 57
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Developmental Anomalies

Outcome Measures

Primary Outcomes (1)

• identification of a causal diagnosis

  identification of genetic etiology

  Through study completion, an average of 2 years

Interventions

blood sample BIOLOGICAL

for patient and its parents

genome sequencing GENETIC

whole genome sequencing

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

child with a suspected genetic disease without an obvious clinical diagnosis and both biological parents

You may qualify if:

• Children (0-6 years old) hospitalized in neonatal intensive care or pediatric intensive care with a suspected genetic disease and without an obvious clinical diagnosis
• Possibility of taking the proband and their 2 biological parents
• Parents affiliated to or beneficiaries of the national health insurance system
• Informed consent signed by the legal representatives of the minor patient
• Ability to understand the study for both biological parents

You may not qualify if:

• Diagnostic hypothesis considered highly probable with an available molecular test having a lower cost than GS
• Individuals who have already had high throughput sequencing (panel, ES)
• Parents protected
• Families where one of the two holders of parental authority is not a biological parent

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

Chu Dijon Bourgogne

Dijon, 21000, France

Location

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 20, 2019
• Study Start: June 23, 2020
• Primary Completion: January 25, 2022
• Study Completion: July 25, 2022
• Last Updated: September 21, 2022

Record last verified: 2022-09

Locations

FR (1)