Development of a Newborn Screening Assay for Angelman Syndrome and Prader-Willi Syndrome

Completed

• Conditions: Prader-Willi Syndrome; Angelman Syndrome
• Interventions: Diagnostic Test: Newborn Screening Assay

• Registration Number: NCT05783791
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

The overall purpose of this project is to establish the capability of screening for Angelman syndrome (AS) and Prader-Willi syndrome (PWS) in public health newborn screening (NBS) programs, with an aim of developing and validating a screening test for AS and PWS.

Detailed Description

This project will have an assay development phase and an assay validation phase.

In the assay development phase, the investigators will develop a method of assessing SNRPN promoter (located in chromosome 15 q11-q13) methylation status using methylation-specific PCR coupled with a melting curve analysis with de-identified leftover DNA from routine newborn screening dried blood samples for severe combined immunodeficiency and spinal muscular atrophy.

In the assay validation phase, the investigators plan to assess the assay sensitivity and specificity using a set of DNA samples extracted from dried blood spots in each following group:

1. Healthy individuals

2. AS patients with genetic testing confirmation that the maternal copy of chromosome 15 q11-q13 is deleted, or that there are two paternal copies of chromosome 15 q11-q13 or imprinting center defect.

3. PWS patients with genetic testing confirmation that the paternal copy of chromosome 15 q11-q13 is deleted, or that there are two maternal copies of chromosome 15 q11-q13 or imprinting center defect.

For participants with AS or PWS, blood samples will be obtained via a self-administered finger prick performed in the participant's home. The participant will mail the sample to the researchers using a provided envelope. If the team is not able to reach the participant after two phone call attempts, the study team may approach them at their next clinic visit to assess interest in study participation. If participants opt to join the study at this clinic visit, the blood sample may be obtained in clinic.

For healthy controls, blood samples will be obtained via a self-administered finger prick, and participants will verbally respond to a brief demographic questionnaire.

Study Timeline

• Study First Submitted: 2023-03-13
• Study First Submitted QC: 2023-03-13
• Study First Posted: 2023-03-24
• Study Start: 2023-04-20
• Primary Completion: 2023-07-21
• Study Completion: 2023-07-21
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-31
• Last Update Posted: 2023-09-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

• Diagnosed with Angelman Syndrome, confirmed by molecular testing (deletion of maternal allele of chromosome 15q11-q13, paternal uniparental disomy, and imprinting center defects)
• Diagnosed with Prader-Willi Syndrome, confirmed by molecular testing (deletion of paternal allele of chromosome 15q11-q13, maternal uniparental disomy, and imprinting center defects)
• Angelman Syndrome or Prader Willi Syndrome: Current patient at UW Health in the Madison, Wisconsin metropolitan area
• Healthy controls 18 years old or older and have not received a diagnosis of Angelman syndrome or Prader Willi syndrome

Exclusion Criteria

• Angelman Syndrome/Prader Willi Syndrome: family requires a translator for medical visits
• Healthy Controls: Participants are unable to consent and complete study procedures in English.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Participants with Angelman Syndrome (AS)	Newborn Screening Assay	AS confirmed by molecular testing
Participants with Prader-Willi Syndrome (PWS)	Newborn Screening Assay	PWS confirmed by molecular testing
Healthy Controls	Newborn Screening Assay	-

Primary Outcome Measures

Name	Time	Method
Sensitivity: Number of True Positive AS Results	1 sample collected from participant either at home or in presence of a study team member at clinic, up to 5 minutes
Sensitivity: Number of True Positive PWS Results	1 sample collected from participant either at home or in presence of a study team member at clinic, up to 5 minutes
Specificity: Number of Healthy Controls With True Negative Results	1 sample collected from participant in presence of a study team member (controls), up to 5 minutes

Trial Locations

Locations (1)

University of Wisconsin School of Medicine and Public Health; 🇺🇸 Madison, Wisconsin, United States