Use of Long Read Genome Sequencing in Patients Suffering From Neurodevelopmental Troubles

Ten families with a child suffering from a neurodevelopmental disease will be recruited by geneticists being part of the CLAD-Ouest. An EDTA blood sample will be taken from the patient and their parents (trio analysis). The blood samples will then be used to extract nucleic acids (DNA).

The blood samples will be sent and centralized to the genetics laboratory of the Nantes University Hospital. The DNA will be extracted and anonymized.

The files generated after DNA sequencing will have as an identification key the anonymization number provided at the time of inclusion of the individual in the study. The raw data and VCF files will be uploaded to the BIRD computing cluster in Nantes, where they will be stored for the duration of the study (2 years). The different university hospitals will then be able to retrieve the data and analyze the variants identified in the patients recruited by their center. A centralized analysis to annotate, filter and interpret the variants will be performed by a group of bioinformaticians and biologists from HUGO (University Hospital from the Grand Ouest). Long-term archiving of the data will be performed at the Nantes University Hospital.

Inclusion criteria

for patients:

• Patient (child or adult) presenting neurodevelopmental troubles strongly suspected to suffer from a rare genetic disease (familial or very severe).
• Negative outcome for short read sequencing of the trio (child and parents).
• Informed consent to the study by the patient (if applicable) or their legal representatives if under-aged or under guardianship.
• Patients benefiting from the social security (French health care system).

Inclusion criteria

for Parents :

• Possible recruitment of both parents matching the inclusion criteria.
• Informed consent form signed for their own participation.
• Parents benefiting from the social security (French health care system).

Exclusion criteria

for patients:

• Genetic predisposition already identified explaining the disease.
• Paients for which the WGS for the trio has not been performed.
• Patients having withdrawn their consent.

Exclusion criteria

fo Parents :

• Pregnant or lactating woman.
• Parents under guardianship or curatorship.
• Parents also presenting a neurodevelopmental deficiency.