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

EXOMEDIANE - Retrospective Study Using High Throughput Sequencing (HTS) on Biological Samples to Improve Genetic Counseling for Patients With Previously Explored Craniofacial Midline Defects.

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.

Study Overview

• Status: Completed
• Conditions: Holoprosencephaly
• Intervention / Treatment: Genetic: NGS

• Study Type: Observational
• Enrollment (Actual): 33

Contacts and Locations

Study Locations

• France
  • Rennes, France
    • CHU Rennes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with an identified genetic abnormality	Number of patients with an identified genetic abnormality	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of new genes identified	Number of new genes identified, and possible recurrence of variants in one or more new genes of interest.	6 months
Pathogenic variants	Percentage of pathogenic variants identified in genes of the SHH pathway	6 months
Modes of transmission of pathogenic variants	Percentage of variants identified according to the different modes of transmission (de novo, autosomal dominant, X-linked, autosomal recessive, oligogenism)	6 months

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Alinoë LAVILLAUREIX, CHU Rennes

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2021
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 6, 2021

Study Registration Dates

• First Submitted: December 28, 2020
• First Submitted That Met QC Criteria: December 30, 2020
• First Posted (Actual): December 31, 2020

Study Record Updates

• Last Update Posted (Actual): December 7, 2021
• Last Update Submitted That Met QC Criteria: December 6, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Nervous System Malformations; Abnormalities, Multiple; Chromosome Disorders; Agenesis of Corpus Callosum; Holoprosencephaly
• Other Study ID Numbers: 35RC20_8894_EXOMEDIANE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No