Molecular Characterization of Patients Affected by Williams Syndrome and Autism.

NCT04095585 | Completed

• 1 other identifier: 2019-WBA
• Study Type: observational
• Target: 6
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Williams Beuren Syndrome; Autism Spectrum Disorder

Keywords

Williams Beuren Syndrome; Autism Spectrum Disorder

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

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)

Interventions

chromosomal microarray analysis (CMA) and whole exome sequencing (WES) GENETIC

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)

Patients presenting with WBS and ASD

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

patients with WBS and ASD.

You may qualify if:

• The diagnosis of WBS was confirmed by fluorescent in situ hybridization.
• All patients met formal ASD criteria
• written informed consent

You may not qualify if:

• None

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Related 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.

  PMID: 31151468 BACKGROUND

MeSH Terms

Conditions

Williams Syndrome; Autism Spectrum Disorder

Interventions

Exome Sequencing

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Aortic Stenosis, Supravalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Whole Genome Sequencing; Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Massimiliano Rossi, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2019
• First Posted: September 19, 2019
• Study Start: September 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 27, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share