Long Read Analysis in Spinal Muscular Atrophy - LOREASI (LOREASI)

December 29, 2025 updated by: University Hospital, Rouen

Detection of Cis Duplications of the SMN1 Gene Using Long-read Analysis to Address a Major Issue in Genetic Counseling for Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is a severe neuromuscular disease caused by deletion of the SMN1 gene, with the most severe form leading to death in children without treatment. Genetic counselling to detect couples where both partners are carriers is particularly important. In some countries, preconception screening is offered. However, some carriers escape detection due to the existence of two copies of the SMN1 gene side-by-side (2+0 genotype). Currently, no molecular genetic methods used for diagnostic purposes can detect these 2+0 genotypes, which pose a significant challenge in genetic counselling.

This study aims to use new technologies based on the analysis of ultra-long molecules to detect side-by-side duplications of the SMN1 gene to detect heterozygous subjects not identified by current techniques and improve genetic counselling.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Spinal Muscular Atrophy (SMA) is a severe autosomal recessive neuromuscular disease, with the most severe form leading to death in children without treatment. Genetic counseling to detect couples where both partners are heterozygous is particularly important. In some countries, preconception screening is offered. However, some individuals' heterozygous status escape detection due to the existence of a cis duplication of the SMN1 gene on the second allele ([2+0] genotype). Currently, no molecular genetic methods used for diagnostic purposes can detect these [2+0] genotypes, which poses a significant challenge in genetic counseling.

The SMN1 gene, responsible for SMA, is located in the 5q11q13 region, which remains poorly understood in the human reference genome ("dark region"). The architecture of this inverted duplicated region favors recombination events that lead to deletions, duplications, and gene conversions. The SMN1 gene, located in the telomeric region, has a very homologous copy, the SMN2 gene, located in the centromeric region. The lack of detailed knowledge about duplication events hinders the development of molecular tools aimed at improving genetic counseling.

This study aims to use new technologies based on the analysis of ultra-long molecules to detect cis duplication of the SMN1 gene. We will assess the usefulness of optical mapping (Bionano) to analyze this complex region.

Study Type

Interventional

Enrollment (Estimated)

27

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

• Adult Subject:

  • Subject with either:

    • 1 or 3 copies of the SMN1 gene (control group) and a variable number of copies of the SMN2 gene
    • 2 copies of the SMN1 gene in cis (2+0 genotype) (test group)
  • Affiliation to French health insurance
  • Signed consent form

Exclusion Criteria

  • Pregnant or breastfeeding women
  • Individuals deprived of liberty by an administrative or judicial decision, or those under guardianship or curatorship

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Control group
subjects carrying 1 or 3 copies of the SMN1 gene and a variable number of copies of the SMN2 gene
Genetic: blood sample
For subjects who agree to participate in the study, a blood sample will be taken (2x5 mL on EDTA) and sent the same day at 4°C to the genetics laboratory at Rouen University Hospital using a carrier that guarantees delivery on D+1
Experimental: Test group
subjects carrying a 2+0 genotype (two copies of the SMN1 gene in cis on one allele and a deletion on the other allele)
Genetic: blood sample
For subjects who agree to participate in the study, a blood sample will be taken (2x5 mL on EDTA) and sent the same day at 4°C to the genetics laboratory at Rouen University Hospital using a carrier that guarantees delivery on D+1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Ability to identify a [2+0] SMN1 genotype
Time Frame: From enrollment until the end of the analyses (36 months)
From enrollment until the end of the analyses (36 months)

Secondary Outcome Measures

Outcome Measure
Time Frame
Ability to perform assembly of ultra-long molecules of DNA
Time Frame: From enrollment until the end of the analyses (36 months)
From enrollment until the end of the analyses (36 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Rouen

Collaborators

Agence de La Biomédecine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2025

Primary Completion (Estimated)

January 15, 2027

Study Completion (Estimated)

January 15, 2027

Study Registration Dates

First Submitted

December 29, 2025

First Submitted That Met QC Criteria

December 29, 2025

First Posted (Estimated)

January 12, 2026

Study Record Updates

Last Update Posted (Estimated)

January 12, 2026

Last Update Submitted That Met QC Criteria

December 29, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023/0154/HP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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