Molecular Characterization of Patients Affected by Williams Syndrome and Autism.

NCT ID: NCT04095585

Last Updated: 2019-09-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 6 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2015-12-31

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

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: OTHER

Study Groups

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.

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

Intervention Type: 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)

Interventions

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)

Intervention Type: GENETIC

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Massimiliano Rossi, MD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

References

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.

Reference Type: BACKGROUND

PMID: 31151468 (View on PubMed)

Other Identifiers

2019-WBA

Identifier Type: -

Identifier Source: org_study_id