WBA: Molecular Characterization of Patients Affected by Williams Syndrome and Autism.
Study Details
Study Description
Brief Summary
Williams Beuren syndrome (WBS) is a multiple malformations/intellectual disability (ID) syndrome caused by 7q11.23 microdeletion and clinically characterized by a typical neurocognitive profile including excessive talkativeness and social disinhibition, often defined as "overfriendliness" and "hypersociability". WBS is generally considered as the polar opposite phenotype to Autism Spectrum Disorder (ASD). Surprisingly, the prevalence of ASD has been reported to be significantly higher in WBS (12%) than in general population (1%). This study aims to investigate the molecular basis of the peculiar association of ASD and WBS. The investigator performed chromosomal microarray analysis and whole exome sequencing in six patients presenting with WBS and ASD, in order to evaluate the possible presence of chromosomal or gene variants considered as pathogenic.
Condition or Disease | Intervention/Treatment | Phase |
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Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Patients presenting with WBS and ASD patients with WBS and ASD. The diagnosis of WBS was confirmed by fluorescent in situ hybridization. All patients met formal ASD criteria. |
Genetic: chromosomal microarray analysis (CMA) and whole exome sequencing (WES)
The investigator evaluated the following hypotheses:
i) atypically large 7q11.23 deletions including additional genes; ii) rare pathogenic variants in genes located within the deletion, in particular GTF2I iii) additional pathogenic copy number variants (CNVs) or rare intragenic pathogenic variants located in other chromosomal regions with various inheritance patterns (autosomal recessive, X-linked, de novo autosomal dominant); given the small number of patients recruited, we focused on rare exonic variants considered to be pathogenic according to the criteria of the American College of Medical Genetics and Genomics (ACMG)
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Outcome Measures
Primary Outcome Measures
- Possible presence of pathogenic chromosomal [Day 0]
Assessed by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) performed on DNA samples collected from the patients.
- Possible presence of gene variants [Day 0]
Assessed by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) performed on DNA samples collected from the patients.
Eligibility Criteria
Criteria
Inclusion Criteria:
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The diagnosis of WBS was confirmed by fluorescent in situ hybridization.
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All patients met formal ASD criteria
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written informed consent
Exclusion Criteria:
- None
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Hospices Civils de Lyon
Investigators
- Principal Investigator: Massimiliano Rossi, MD, Hospices Civils de Lyon
Study Documents (Full-Text)
None provided.More Information
Publications
- 2019-WBA