Molecular Characterization of Patients Affected by Williams Syndrome and Autism.

Autism Spectrum Disorder Clinical Trial

— WBA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04095585
• Other study ID #: 2019-WBA
• Status: Completed
• Start date: September 2014
• Est. completion date: December 2015

Study information

• Verified date: September 2019
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive
• Syndrome
• Williams Beuren Syndrome
• Williams Syndrome

Intervention

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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

References & Publications (1)

Masson J, Demily C, Chatron N, Labalme A, Rollat-Farnier PA, Schluth-Bolard C, Gilbert-Dussardier B, Giuliano F, Touraine R, Tordjman S, Verloes A, Testa G, Sanlaville D, Edery P, Lesca G, Rossi M. Molecular investigation, using chromosomal microarray and whole exome sequencing, of six patients affected by Williams Beuren syndrome and Autism Spectrum Disorder. Orphanet J Rare Dis. 2019 May 31;14(1):121. doi: 10.1186/s13023-019-1094-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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