Finding genetic causes of cleft lip and palate using whole exome sequencing

Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing GENEPIC

This project will try to find genetic changes that cause non‑syndromic cleft lip and/or palate by sequencing the protein‑coding parts of DNA in patients seen at the Amiens center.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sex: All
• Sponsor: Centre Hospitalier Universitaire, Amiens (other)
• Locations: 1 site (Amiens)
• Trial ID: NCT03065686 on ClinicalTrials.gov

What this trial studies

Researchers will perform whole exome sequencing (WES) on precisely phenotyped patients with non‑syndromic cleft lip and/or palate who are followed at the CHU Amiens Picardie multidisciplinary center. Eligible participants are those with NSCL/P of unknown cause who hold national health insurance, while cases with a known genetic cause or an IRF6 mutation are excluded. The project searches for rare or novel coding variants that may explain individual cases or reveal new disease genes, building on prior WES successes in craniofacial syndromes. Candidate variants will be interpreted alongside clinical phenotype and existing gene pathway knowledge to prioritize findings for follow‑up.

Who should consider this trial

Good fit: Ideal candidates are patients with non‑syndromic cleft lip and/or palate of unknown cause who are followed at CHU Amiens Picardie and who hold national health insurance.

Not a fit: Patients with a known genetic cause of their cleft (including IRF6 mutations), those with syndromic clefts, and individuals for whom no causative variant is identified are unlikely to gain direct clinical benefit from this project.

Why it matters

Potential benefit: If successful, the work could identify genetic causes for some patients, improving diagnosis, genetic counseling, and guiding future research.

How similar studies have performed: Whole exome sequencing has successfully identified causal genes in several craniofacial syndromes (for example Freeman‑Sheldon and Miller syndromes) and has been applied in cleft research, though non‑syndromic clefting remains genetically heterogeneous and many cases remain unexplained.

Eligibility criteria

Inclusion Criteria:

* Subject with a NSCL/P or CL/P of unknown etiology,
* national health care insurance holders

Exclusion Criteria:

* Subject with a CL/P of known etiology,
* Subject with a NSCL/P and an IRF6 mutation

Where this trial is running

Amiens

• CHU Amiens Picardie — Amiens, France (RECRUITING)

Study contacts

• Principal investigator: Bénédicte DEMEER, MD — CHU Amiens
• Study coordinator: Bénédicte DEMEER, MD

Conditions: Cleft Lip and Palate, CL/P, WES