Molecular Characterization of Patients Affected by Williams Syndrome and Autism.

Study Overview
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Brief Summary
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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.

Official Title
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Molecular Investigation, Using Chromosomal Microarray and Whole Exome Sequencing, of Patients Affected by Williams Beuren Syndrome and Autism Spectrum Disorder

Conditions
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Williams Beuren Syndrome, Autism Spectrum Disorder

Intervention / Treatment
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* Genetic: chromosomal microarray analysis (CMA) and whole exome sequencing (WES)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The diagnosis of WBS was confirmed by fluorescent in situ hybridization. All patients met formal ASD criteria written informed consent Exclusion Criteria: None
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients presenting with WBS and ASD<br>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)<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Possible presence of pathogenic chromosomal | Assessed by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) performed on DNA samples collected from the patients. | Day 0 | 
| Possible presence of gene variants | Assessed by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) performed on DNA samples collected from the patients. | Day 0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Williams Beuren Syndrome, Autism Spectrum Disorder