Retrospective Study Using Next Generation Sequencing (NGS) on Biological Samples to Improve Genetic Counseling for Patients With Previously Explored Craniofacial Midline Defects.

NCT04691414 | Completed

• 1 other identifier: 35RC20_8894_EXOMEDIANE
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Holoprosencephaly, or HPE, is the most common congenital cerebral malformation in humans and the most severe of a group of pathologies related to a deficiency of the SHH signalling pathway (Sonic Hedgehog SHH-D). It is characterized by severe cerebral and craniofacial abnormalities. The regulation of SHH concentration is therefore crucial for correct craniofacial development. Despite the recent identification of about 20 genes, 70% of cases of EHPE and craniofacial midline abnormalities of genetic origin do not have a molecular diagnosis. It is therefore important to continue the search for new candidate genes to improve the understanding of brain and facial development and to improve genetic counseling for these families. The development of Next-Generation Sequencing (NGS) technologies opens up the possibility of studying the exome or even the genome in a single manipulation. The latter type of analysis is particularly well suited to the discovery of new genes and will therefore improve the care of patients and their families.

Conditions

Holoprosencephaly

Outcome Measures

Primary Outcomes (1)

• Number of patients with an identified genetic abnormality

  Number of patients with an identified genetic abnormality

  6 months

Secondary Outcomes (3)

• Number of new genes identified

  6 months

• Pathogenic variants

  6 months

• Modes of transmission of pathogenic variants

  6 months

Interventions

NGS GENETIC

next-generation sequencing on preexisting samples

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

17 Trios : 17 patient with Craniofacial Midline Facial Anomalies and both parents already diagnosed in routine care. Blood samples for all trio must be available in the biobank and parents and patient if he's not a minor have to accept genetic analyses.

You may qualify if:

• Patients with Craniofacial Midline Facial Anomalies (CMFLA) collected for genetic analysis
• Patients and relatives for whom consent for research-related genetic testing is available. A "trio" - patient and both parents is required for analysis of variant segregation and determination of mode of transmission.
• For patients who are minors, parental authority(ies) who have given consent for research genetic testing.
• Affiliation to a social security scheme
• Patient and parents do not object to their participation in the research.
• In the case of a patient who has reached the age of majority since the initial consent was obtained, a patient who has given consent to proceed with genetic analyses for research purposes.

You may not qualify if:

• adults subject to legal protection (safeguard of justice, curatorship, guardianship), persons deprived of liberty.

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (1)

CHU Rennes

Rennes, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

national biobank

MeSH Terms

Conditions

Holoprosencephaly

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Agenesis of Corpus Callosum; Nervous System Malformations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Alinoë LAVILLAUREIX

  CHU Rennes

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 28, 2020
• First Posted: December 31, 2020
• Study Start: February 10, 2021
• Primary Completion: December 1, 2021
• Study Completion: December 6, 2021
• Last Updated: December 7, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)