Clinical trial NCT04691414: Retrospective Study Using Next Generation Sequencing (NGS) on Biological Samples to Improve Genetic Counseling for Patients With Previously Explored Craniofacial Midline Defects.
Official title: EXOMEDIANE - Retrospective Study Using High Throughput Sequencing (HTS) on Biological Samples to Improve Genetic Counseling for Patients With Previously Explored Craniofacial Midline Defects.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Holoprosencephaly
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2020-12-31
Enrollment: 33
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients with an identified genetic abnormality
timeFrame: 6 months
Secondary outcomes:
measure: Number of new genes identified
timeFrame: 6 months
measure: Pathogenic variants
timeFrame: 6 months
measure: Modes of transmission of pathogenic variants
timeFrame: 6 months
Other outcomes:
Locations:
city: Rennes
country: France
facility: CHU Rennes
Study officials:
affiliation: CHU Rennes
name: Alinoë LAVILLAUREIX
role: PRINCIPAL_INVESTIGATOR
References: