High Depth Exome Sequencing on DNA From a Salivary Sample by Mouth Smear. (SEPASA)

Evaluation of the Diagnostic Performance of High-depth Exome Sequencing on DNA From a Salivary Sample by Oral Smear in the Etiological Assessment of Patients With a Syndromic Neurodevelopmental Disorder or an Intellectual Development Disorder and for Which the Sequencing of the Genome on Blood Has Proved Inconclusive.

Despite technological advances, a genetic etiology has been identified in only about 50% to 60% of patients with Neurodevelopmental disorders (NDDs), with a higher diagnostic yield in the syndromic NDD and IDD subgroups. However, identifying a precise etiological diagnosis is essential to optimize patient care, clarify their prognosis, consider targeted therapies, refer families to appropriate resources and support, and provide genetic counseling to relatives. The tests typically offered as part of the etiological assessment of syndromic NDDs and IDD include DNA microarray analysis, testing for fragile X syndrome and genome sequencing from a blood sample. When this assessment remains negative, the cause usually remains unknown.

Mosaic genomic abnormalities (or post-zygotic variations) are a common cause of negative results in current diagnostic genetic tests and represent a field of research that has yet to be fully explored outside of skin disorders. Identifying mosaic genomic abnormalities remains technically complex due to the difficulty of detecting low levels of mosaicism and limited access to the tissue of interest when the variation is absent from blood tissue.

High-depth exome sequencing is the technique of choice for detecting low levels of mosaicism. In the case of NNDs, as the affected tissue is not available, the buccal epithelium is an interesting alternative to blood, as it is easily accessible and inexpensive.

The objective of our study is to evaluate the diagnostic yield of high-depth exome sequencing technology on a DNA extracted from a buccal swab in the etiological assessment of patients with IDD or syndromic NDD whose reference analysis (genome sequencing on blood) proved inconclusive.

Study Overview

• Status: Not yet recruiting
• Conditions: Neurodevelopmental Disorders; Intellectual Developmental Disorder
• Intervention / Treatment: Diagnostic test: genetic

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Juliette PIARD, Pr; Phone Number: 33381218187; Email: jpiard@chu-besancon.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Men and women of all ages with syndromic neurodevelopmental disorder (NDD) or intellectual developmental disorder (IDD) and a trio genome sequencing on blood inconclusive

Description

Inclusion Criteria:

• Patient with syndromic neurodevelopmental disorder (NDD) or intellectual developmental disorder (IDD)
• Trio genome sequencing on blood inconclusive
• Men and women
• All ages
• No objection to participating in the study
• Affiliation with a French social security system or beneficiary of such a system

Exclusion Criteria:

• Pregnant women and nursing mothers
• Persons deprived of their liberty by judicial or administrative decision; persons undergoing compulsory psychiatric care; persons admitted to a health or social care facility for purposes other than research
• Subjects who are in the exclusion period of another study or listed in the "national volunteer registry"
• Genetic cause identified in the preliminary etiological assessment
• Phenocopy: other likely non-genetic cause of TND (perinatal anoxia, infection, trauma, etc.)
• Patients without health insurance
• Patients unlikely to cooperate with the study and/or anticipated low cooperation by the investigator

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of a defined genetic cause by demonstrating at least one variation of class 4 (probably pathogenic) or 5 (pathogenic) according to the ACMG classification explaining the patient's symptoms.	2 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurodevelopmental Disorders; Intellectual Disability
• Other Study ID Numbers: 2026/1030

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