Molecular Characterization of Patients Affected by Williams Syndrome and Autism. (WBA)

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

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.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder; Williams Beuren Syndrome
• Intervention / Treatment: Genetic: chromosomal microarray analysis (CMA) and whole exome sequencing (WES)

• Study Type: Observational
• Enrollment (Actual): 6

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

patients with WBS and ASD.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Massimiliano Rossi, MD, Hospices Civils de Lyon

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 16, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (Actual): September 19, 2019

Study Record Updates

• Last Update Posted (Actual): September 27, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Autism Spectrum Disorder; Williams Beuren Syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Aortic Valve Disease; Heart Valve Diseases; Intellectual Disability; Neurodevelopmental Disorders; Chromosome Disorders; Aortic Valve Stenosis; Aortic Stenosis, Supravalvular; Syndrome; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Williams Syndrome
• Other Study ID Numbers: 2019-WBA

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