Advancing Neurogenetic Diagnoses Through Long-Read Sequencing

NCT07665554 | Not Yet Recruiting

• 1 other identifier: CHUBX 2025/017
• Study Type: interventional
• Target: 304
• Locations: 1 country
• Sites: 2

Brief Summary

Nucleotide repeats emerge as one of the most prolific classes of genetic variations. They have the propensity to in-crease in length across generations, and have been implicated in at least 65 known neurological/ neurodevelop-mental and neuromuscular conditions. Simultaneous analysis of all these nucleotide repeats is now possible through the cutting-edge methodologies recently developed that are the long-read sequencing and the optical genome mapping. Investigator propose to test these methodologies in patients carrying expansions in those repeats and to determine the capacity of these technics to detect novel repeats in patients with no genetic diagnosis yet.

Conditions

Neurogenetic Diseases

Keywords

long read sequencing; genetic diagnosis; cytogenetics; nucletotide repeat expansion; neurogenetic disease

Outcome Measures

Primary Outcomes (2)

• Diagnosis by NGS technology

  The first primary endpoint is the ability of the proposed Next-Generation Sequencing (NGS) technology to establish the diagnosis of each neurogenetic disease studied, defined as the presence or absence of the disease, in comparison with the currently used reference method (gene-specific Polymerase Chain reaction (PCR)). NGS analysis will be performed blinded to the results previously obtained on the same samples using the reference technique, taking into account the disease under investigation and the number of repeat amplifications.

  Inclusion visit

• Molecular diagnosis

  Identification a molecular diagnosis in families undergoing a diagnostic odyssey, by demonstrating both the presence of repeat expansions in affected family members and the absence of such expansions in unaffected individuals within the same family.

  Inclusion visit

Secondary Outcomes (2)

• New complex haplotypes

  Inclusion visit

• Deleterious biological effect

  Inclusion visit

Study Arms (3)

Control

OTHER

Procedure: Skin biopsy; Procedure: blood sampling

Diagnosed family

OTHER

Procedure: blood sampling

Undiagnosed family

OTHER

Procedure: Skin biopsy; Procedure: blood sampling

Interventions

Skin biopsy PROCEDURE

Skin biopsy is a minimally invasive procedure. It will be performed during a follow-up visit. The skin biopsy is a technically simple procedure performed using a 5-mm diameter punch under local anesthesia. The procedure can be carried out in a consultation room under strict aseptic conditions and takes a total of approximately 15 minutes.The biopsy may be performed at several anatomical sites but is generally carried out on the inner aspect of the arm. It will be performed by a resident or a senior registrar. The skin biopsy sample is placed in a vial containing physiological saline and sent at room temperature.

Control; Undiagnosed family

blood sampling PROCEDURE

Blood sampling is a routine biological procedure performed under the same conditions as during a follow-up consultation. Pain, redness, or bleeding may occur at the puncture site. If the required samples are not already available, they will be collected. The maximum volumes collected will be as follows and will represent a total volume of less than two tablespoons (for participants weighing less than 30 kg, only one tube of each type will be collected)

Control; Diagnosed family; Undiagnosed family

Eligibility Criteria

• Age: 6 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• All participants :
• Participants affiliated with or beneficiaries of a social security scheme
• Participants who speak French
• Participants aged ≥ 6 and ≤ 60 years
• For patients requiring a new sample:
• Free and informed consent, signed by the parents or the holder of parental authority for patients under the age of 18
• Free and informed consent, signed by the patient's representative for adults under guardianship
• Free and informed consent, signed by the adult patient
• For diagnosed patients :
• DeoxyriboNucleic Acid (DNA) sample from a subject carrying a nucleotide repeat expansion in one of the selected genes.
• DNA available in sufficient quantity (5-10 µg) or patient agreeing to a blood draw from which DNA will be extracted.
• DNA extraction methods known and validated by the steering committee (see paragraph 7).
• For participants from undiagnosed families :
• o Index cases:
• Patient affected by a neurological disease candidate for these repeats, for which genomic data did not reveal mutations or expansions in known genes.

You may not qualify if:

• For all participants:
• Refusal to participate in research: Refusal to provide informed consent or opposition to the use of these samples.
• By the parents or the holder of parental authority for patients under the age of 18
• By the patient's representative for adults under guardianship
• By the adult patient This opposition from the patient must be communicated to the site investigator within a maximum of one month after the information note has been sent. If the letter confirming consent is returned due to an incorrect address, the patient will not be included.
• Degraded DNA or average size \< 30 kb

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (2)

CHU Bordeaux - Hôpital Pellegrin

Bordeaux, France, 33076, France

Location

AP-HP Hôpital Pitié-Salpêtrière

Paris, France, 75013, 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 Officials

• Cyril GOIZET, PROF

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cyril GOIZET, PROF

CONTACT

+335 56 79 59 52; cyril.goizet@chu-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: June 24, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: June 24, 2026

Record last verified: 2026-06

Locations

FR (2)