Methylome Study in Sporadic Limb Malformations

NCT05555225 | Not Yet Recruiting

• 2 other identifiers: 2021_05242022-A01441-42
• Study Type: observational
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

Some limb malformations are known to be sporadic (non hereditary). For these malformations, no molecular cause was identified, even after whole genome sequencing. Methylation of CpG islands is an epigenetic process which is usually not transmitted to the descents. We hypothesize that sporadic limb malformations may be due to a methylation anomaly. This study will include patients with Amelia or Femur Fibula Ulna Syndrome. With patients consent, we will study the methylome on DNA samples already available in our laboratory. Each patient sample will be paired to a control of same tissue, age and sex. By bioinformatics comparison, we will identify differentially methylated candidate regions.

Conditions

Amelia; Femur Fibula Ulna Syndrome

Keywords

Amelia; Femur-Fibula-Ulna Syndrome; Methylation; Limb development; Gene regulation

Outcome Measures

Primary Outcomes (1)

• Differentially Methylated Regions

  through study completion an average of 3 years

Study Arms (3)

Patients with amelia

Patients with severe hypoplasia or agenesia of at least two limbs who gave their consent for the research and for whom a DNA sample is available in our laboratory

Other: Methylome

Patients with Femur-Fibula-Ulna Syndrome

Patients with anomaly of at least one femur, one fibula and with oligodactyly who gave their consent for the research and for whom a DNA sample is available in our laboratory.

Other: Methylome

Healthy subjects

Healthy subjects used as controls, who gave their consent for the research and for whom a DNA sample is available in our laboratory.

Other: Methylome

Interventions

Methylome OTHER

Epigenetic study : analysis of DNA methylation

Healthy subjects; Patients with Femur-Fibula-Ulna Syndrome; Patients with amelia

Eligibility Criteria

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

Study Population

DNA samples were obtained from the molecular biology laboratory of Lille university hospital. All patients exhibiting amelia or Femur-Fibula-Ulna Syndrome and with enough DNA available in the lab could be included.

You may qualify if:

• Specific consent for this study
• DNA available in the laboratory
• For amelia : agenesia of 2 or 4 limbs
• For Femur-Fibula-Ulna Syndrome : hypoplasia or agenesia of the femur uni or bilateral with hypoplasia or agenesia or bowing of the fibula and/or of the ulna

You may not qualify if:

• No consent
• No available DNA or poor quality of the DNA sample
• Patient under tutorship
• Pregnancy or nursing mother
• Patient non covered by the French social security

Sponsors & Collaborators

• University Hospital, Lille: lead
• Groupement Interrégional de Recherche Clinique et d'Innovation: collaborator

MeSH Terms

Conditions

Ectromelia; Femur fibula ulna syndrome

Interventions

Epigenome

Condition Hierarchy (Ancestors)

Limb Deformities, Congenital; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Genome; Genetic Structures; Genetic Phenomena

Study Officials

• Perrine BRUNELLE, MD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Perrine BRUNELLE, MD

CONTACT

0320445962; perrine.brunelle@chru-lille.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2022
• First Posted: September 26, 2022
• Study Start: April 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 16, 2024

Record last verified: 2024-05