Molecular Characterization of Patients Affected by Williams Syndrome and Autism.

Overview

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.

Full Title of Study: “Molecular Investigation, Using Chromosomal Microarray and Whole Exome Sequencing, of Patients Affected by Williams Beuren Syndrome and Autism Spectrum Disorder”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Other
  • Study Primary Completion Date: November 2015

Interventions

  • 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)

Arms, Groups and Cohorts

  • 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.

Clinical Trial Outcome Measures

Primary Measures

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

Participating in This Clinical Trial

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
  • Gender Eligibility: All

    Minimum Age: N/A

    Maximum Age: N/A

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Hospices Civils de Lyon
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • Massimiliano Rossi, MD, 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.

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