Genetic Newborn Screening for Rare Diseases Within the Screen4Care Project: the French Participation

Recruiting

• Conditions: Genetic Predisposition to Disease
• Interventions: Biological: Blood samples; Diagnostic Test: DBS card

• Registration Number: NCT06528548
• Lead Sponsor: Centre Hospitalier Universitaire Dijon

Brief Summary

Newborn screening (NBS) programs are established to screen infants shortly after birth for conditions that are treatable, but not always clinically evident in the newborn period. Traditionally metabolic markers in dried blood spots (DBS) are used to diagnose these diseases. NBS detects diseases for which early diagnosis and treatment reduce long-term complications and mortality. The screening programs vary widely across Europe: Italy currently screens for 48 diseases, whereas Germany screens for 19 diseases and France screens for 14.

Through advances of genetic testing technologies, it is nowadays also possible to use DNA sequencing from DBS to test for genetic diseases. In parallel, the number of diseases, for which treatments are available are constantly increasing.

This study aims to explore the use of more extensive genetic testing by panel-based next generation sequencing to screen newborns for treatable genetic diseases. Genetic newborn screening (gNBS) is one of the pillars and the "core" of WP3 of S4C European Innovative Medicines Innitiative (IMI).

project; indeed, this work package (WP3) aims to explore the use of gNBS in newborns as a gateway to shorten the diagnostic path and offer the opportunity for early treatment. gNBS will adopt different strategies interrogating currently treatable rare diseases (RDs) (TREAT-panel-approach) (Step1). The TREAT-panel will include 245 disease genes that are related to treatable genetic disorders, prioritising those with early onset and where natural history key elements are known.

Genome sequencing (GS) will be offered to symptomatic patients to identify known gNBS-escaped RDs and novel genes/phenotypes (Step 2). More rarely, it could identify a candidate gene not yet known in human pathology.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-23
• Study First Submitted QC: 2024-07-26
• Study First Posted: 2024-07-30
• Status Verified: 2025-01
• Study Start: 2025-01-13
• Last Update Submitted: 2025-01-21
• Last Update Posted: 2025-01-23
• Primary Completion: 2027-09
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1060

Inclusion Criteria

For step 1

• Newborns less than 28 days, born in the maternity of Dijon University Hospital
• Informed consent signed by both parents/legal guardian/minor parents with parental authority over their child to participate in the present S4C study
• For the exploratory interviews, voluntary parents to participate

For step 2

• Early symptoms (within 24 months of life) suggestive of a rare genetic disease in infants resulted negative at the TREAT-panel gNBS
• Informed consent signed by both parents to participate in GS study

Exclusion Criteria

Both steps

• Parents subject to a measure of legal protection (guardianship, tutorship)
• Parents subject to a court order
• Parents incapable of expressing consent
• Parents who is not affiliated with the national health insurance system

For step 1 - Any newborn in which clinical considerations preclude drawing 1.0 ml of blood for the additional blotting paper

For step 2

• Infants not screened by TREAT-panel gNBS

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
tios	Blood samples	infants resulted negative at the TREAT-panel gNBS at the step 1 and their parents
participants	DBS card	1000 newborns are expected to take part in step 1

Primary Outcome Measures

Name	Time	Method
Number of couples who will accept to participate to the TREAT-panel gNBS	Through study completion, on average of 9 months
Number of newborns in whom a pathogenic or likely pathogenic variant in appropriate inheritance model will be identified through TREAT-panel	Through study completion, on average of 9 months
Number of child resulted negative at the TREAT-panel gNBS who develop early symptoms leading to the diagnosis a rare genetic disease by GS	Through study completion, on average of 26 months

Trial Locations

Locations (1)

Chu Dijon Bourgogne; 🇫🇷 Dijon, France