NCT07332702

Long Read Analysis in Spinal Muscular Atrophy - LOREASI

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: University Hospital, Rouen · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Spinal Muscular Atrophy (SMA)

Interventions

Type	Name	Description
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

Timeline

• Start date: 2025-05-15
• Primary completion: 2027-01-15
• Completion: 2027-01-15
• First posted: 2026-01-12
• Last updated: 2026-01-12

Locations

1 site across 1 country: France