Use of Long Read Genome Sequencing in Patients Suffering From Neurodevelopmental Troubles

NCT05643274 | Completed

• 1 other identifier: RC22_0373
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 5

Brief Summary

Patients with neurodevelopmental diseases and their families need to identify the genetic cause of the disease to allow for recognition of the disability, genetic counseling, and possible hope for participation in therapeutic research studies. Access to high-throughput genomic exome or genome analysis allows the identification of a genetic cause for approximately half of the patients. However, families with no result or with a variant of unknown significance after these tests may find themselves in a new diagnostic impasse. The high-throughput sequencing used today generates sequences of the order of 100 base pairs (so-called "short read" sequencing). This allows an analysis of about 90% of the genome. However, many regions are not accessible in regions of interest for the genetic diagnosis of rare diseases. Long fragment sequencing generates sequences that are about 20 times larger and its use has recently made it possible to sequence the human genome almost completely (https://www.science.org/doi/10.1126/science.abj6987). The main contribution lies in the analysis of complex regions of the genome such as segmental duplications or centromeric regions. It is likely that this technology increases the sensitivity of detection of genetic variants in patients with genetic diseases. Its contribution should be studied in patients for whom no genetic cause has been identified by classical techniques. This study aim to investigate the contribution of long fragment genome sequencing.

Conditions

Genetic Disease; Neurologic Disorder; Developmental Delay Disorder; Growth Disorders

Keywords

long read sequencing; rare genetic diseases; neurodevelopmental diseases; diagnostic

Outcome Measures

Primary Outcomes (1)

• Use of long read sequencing in patients suffering from a neurodevelopmental disease without pathogenic or probably pathogenic variation identified by short read sequencing

  Identification of a genetic diagnosis : detection of one or several variant(s) - nucleotidic, change in copy number, structural variants- of class 4 or 5 (probably pathogenic or pathogenic), explaining the genetic origin of the neurodevelopmental pathology

  through study completion, an average of 2 years

Secondary Outcomes (1)

• Analysis of the implementation of the long read sequencing of trios (patients and parents)

  through study completion, an average of 2 years

Study Arms (1)

Participants

Patients with neurodevelopmental disease and their both parents

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient with neurodevelopmental diseases and their both parents

You may qualify if:

• Patient (child or adult) presenting neurodevelopmental troubles strongly suspected to suffer from a rare genetic disease (familial or very severe).
• Negative outcome for short read sequencing of the trio (child and parents).
• Informed consent to the study by the patient (if applicable) or their legal representatives if under-aged or under guardianship.
• Patients benefiting from the social security (French health care system).
• Informed consent form signed for their own participation.
• Parents benefiting from the social security (French health care system).

You may not qualify if:

• Genetic predisposition already identified explaining the disease.
• Paients for which the WGS for the trio has not been performed.
• Patients having withdrawn their consent.
• Pregnant or lactating woman.
• Parents under guardianship or curatorship.
• Parents also presenting a neurodevelopmental deficiency.

Sponsors & Collaborators

• Nantes University Hospital: lead
• Rennes University Hospital: collaborator
• University Hospital, Angers: collaborator
• University Hospital, Brest: collaborator
• University Hospital, Tours: collaborator

Study Sites (5)

Brest University Hospital

Brest, Finistère, 29000, France

Location

Rennes University Hospital

Rennes, Ille-et-Vilaine, 35000, France

Location

Tours University Hospital

Tours, Indre-et-Loire, 37000, France

Location

Nantes University Hospital

Nantes, Loire-Atlantique, 44093, France

Location

Angers University Hospital

Angers, Maine-et-Loire, 49000, France

Location

MeSH Terms

Conditions

Genetic Diseases, Inborn; Nervous System Diseases; Developmental Disabilities; Growth Disorders; Disease

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stéphane BEZIEAU, MD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: December 8, 2022
• Study Start: December 19, 2022
• Primary Completion: March 8, 2023
• Study Completion: March 8, 2024
• Last Updated: April 24, 2024

Record last verified: 2024-04

Locations

FR (5)