Quantification of Elastin Markers Synthesis in Williams-Beuren Syndrome and 7q11.23 Micro-duplication Syndrome

Overview

Introduction: Williams-Beuren syndrome is a rare genetic disorder caused by a 7q11.23 microdeletion. The phenotype associates vasculopathy (arterial stenosis, hypertension), dimorphism and intellectual disability. Microdeletion includes several genes: ELN encodes for elastin and the haplo-insufficiency (only 1 functional copy) causes vasculopathy. The primary objective is to quantify plasma and urinary levels of elastin peptides in Williams-Beuren patients and 7q11.23 micro-duplication syndrome patients in order to correlate the levels of these markers with the number of copies of ELN gene (proportional positive relationship "gene copy number – circulating levels of markers) Materials and Methods: This prospective study will be carried out in Lyon at the "Hôpital Femme-Mère-Enfant" for 2 years. 3 groups of patients will be studied: Williams-Beuren patients (N=20), micro-duplication 7q11.23 syndrome patients (N=10) and healthy patients (N=60). Subjects will be followed for 1 day. Clinical examination (weight, height, blood pressure) and biological sample collection (blood and urine sample) will be carry out for Williams Beuren and micro-duplication 7q11.23 patients group. A large majority of visits will be part of patients' usual care. A large part of patients are systematically seen in consultation once a year. For healthy group, only biological sample collection will be carry out. The PE concentrations will be assessed and compared between the three groups of patients.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Other
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 2021

Interventions

  • Biological: Physical examination and Urine and blood samples
    • Only one visit for each participant : A large majority of visits will be part of patients’ usual care Medical examination : birth, weight, gender, blood pressure, medical history Urine and blood samples
  • Biological: Urine and blood samples
    • Only one visit for each participant Medical history Urine and blood samples

Arms, Groups and Cohorts

  • Other: Williams Beuren
    • Subjects aged from 3 months to 60 years with a diagnosis confirmed with FISH of Williams Beuren syndrome.
  • Other: Micro-duplication 7q11.23
    • Subjects aged from 3 months to 60 years with a diagnosis confirmed with CGHarray of micro-duplication 7q11.23 syndrome.
  • Other: Healthy Group
    • Subjects without cardiovascular and neurological medical history.

Clinical Trial Outcome Measures

Primary Measures

  • Plasma level of elastin peptides (PE)
    • Time Frame: 1 day
    • To quantify plasma level of elastin peptides in participants in order to correlate the levels of these markers with the number of copies of ELN gene (proportional positive relationship “gene copy number – circulating levels of markers). The primary endpoint will be assessed by measuring the blood level of PE between groups
  • Urinary level of elastin peptides (PE)
    • Time Frame: 1 day
    • To quantify urinary level of elastin peptides in participants in order to correlate the levels of these markers with the number of copies of ELN gene (proportional positive relationship “gene copy number – circulating levels of markers). The primary endpoint will be assessed by measuring the urinary level of PE between groups

Secondary Measures

  • Correlation between blood level of PE and cardiovascular involvement in patients.
    • Time Frame: 1 day
    • Blood level of PE will be correlated with the presence / severity of cardiovascular disease
  • Correlation between urinary level of PE and cardiovascular involvement in patients.
    • Time Frame: 1 day
    • Urinary level of PE will be correlated with the presence / severity of cardiovascular disease
  • Blood level of PE in treated and untreated minoxidil patients
    • Time Frame: 1 day
    • Blood levels of PE in the samples of patients who participated in the minoxidil clinical trial will be compare to those of participants of this study
  • Urinary level of PE in treated and untreated minoxidil patients
    • Time Frame: 1 day
    • Urinary levels of PE in the samples of patients who participated in the minoxidil clinical trial will be compare to those of participants of this study

Participating in This Clinical Trial

Inclusion Criteria

  • Age : from 3 months to 60 years old – Williams Beuren group : Diagnosis confirmed with FISH – Micro-duplication 7q11.23 group : Diagnosis confirmed with CGHarray – Healthy Group : no cardiovascular and neurological medical history – Informed consent Exclusion Criteria:
  • No social insurance – Subject under judicial protection – Subject participating in another research including an exclusion period still in progress
  • Gender Eligibility: All

    Minimum Age: 3 Months

    Maximum Age: 60 Years

    Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

    Investigator Details

    • Lead Sponsor
      • Hospices Civils de Lyon
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Contact(s)
      • Massimiliano ROSSI, Dr, 04 27 85 55 72, Massimiliano.rossi@chu-lyon.fr

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