Holoprosencephaly
Conditions
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.
Interventions
GENETICNGS
next-generation sequencing on preexisting samples
Sponsors
Rennes University Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with an identified genetic abnormality | 6 months | Number of patients with an identified genetic abnormality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of new genes identified | 6 months | Number of new genes identified, and possible recurrence of variants in one or more new genes of interest. |
| Pathogenic variants | 6 months | Percentage of pathogenic variants identified in genes of the SHH pathway |
| Modes of transmission of pathogenic variants | 6 months | Percentage of variants identified according to the different modes of transmission (de novo, autosomal dominant, X-linked, autosomal recessive, oligogenism) |
Countries
France
Outcome results
None listed