Angelman Syndrome, Prader-Willi Syndrome
Conditions
Keywords
Newborn Screening, Assay, Public Health
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.
Interventions
DIAGNOSTIC_TESTNewborn Screening Assay
The assay developed in this study is determined to be FDA regulated as an exempt diagnostic device. In this study, the testing involved with this assay fulfills the following criteria: * Is noninvasive * Does not require an invasive sampling procedure that presents significant risk (the finger prick is minimal risk) * Does not by design or intention introduce energy into a subject, and * Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure, as participants will not receive results in this study.
Sponsors
Ultragenyx Pharmaceutical Inc
University of Wisconsin, Madison
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Outcome results
None listed