Diagnosis of Prader-Willi Syndrome and Angelman Syndrome

Dr. Pao-Lin Kuo (Department of Obstetrics and Gynecology)

In a retrospective study, data were assessed from cases regarding PWS/AS that underwent molecular diagnosis at the National Chen-Kung University Hospital, Tainan, Taiwan, between January 2001 and December 2014.

Study Overview

• Status: Completed
• Conditions: Mental Disorder; Fetus Disorder

Detailed Description

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct syndromes of developmental impairment that result from loss of the expression of imprinted genes on the q11-q13 region of chromosome 15 (15q11-q13). Approximately 70%--75% of individuals affected with PWS and AS have an interstitial deletion of 15q11-q13. Regarding the remaining individuals with PWS, maternal uniparental disomy is the cause in 20% of cases, imprinting errors in 3% of cases, and chromosomal translocation in approximately 1% of cases. Regarding the remaining cases of AS, paternal uniparental disomy accounts for 2% of cases and mutations in the UBE3A gene for 20% of cases.The PWS/AS critical region was examined by fluorescence in situ hybridization (FISH), methylation-specific PCR (M-PCR), and methylation-specific multiplex-ligation dependent probe amplification(MS-MLPA). In a retrospective study at the National Chen-Kung University Hospital,Tainan, Taiwan, data were reviewed from cases that were referred for molecular diagnosis between January 1, 2001, and December 31, 2014.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 70428
    • National Cheng-Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

During January 1, 2001, and December 31, 2014, cases were referred for molecular diagnosis such as individual with clinical features related to Prader-Willi syndrome or Angelman syndrome ; fetus with deletion or duplication of chromosome 15q11.2-q13 visible by the microscope; fetus whose mother or father has chromosomal abnormality involving 15q11.2-q13 and fetus with mosaic trisomy 15

Description

Inclusion Criteria:

• Individual with clinical features related to Prader-Willi syndrome or Angelman syndrome;
• Fetus with suspicious deletion or duplication of chromosome 15q11.2-q13 visible by the microscope;
• Fetus whose mother or father has chromosomal abnormality involving 15q11.2-q13
• Fetus with mosaic trisomy 15

Exclusion Criteria:

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
M-PCR(methylation-specific PCR)	Abnormal pattern of M-PCR can identify PWS or AS	up to 4 weeks after diagnosis
FISH(fluorescent in-situ hybridization)	A "FISH" test will identify PWS/AS due to a deletion, but it will not identify those by UPD or an imprinting error.	up to 4 weeks after diagnosis
STR(short tandem repeat) for UPD (uniparental disomy)	A '"STR" test can identify PWS/AS duo to paternal or maternal UPD.	up to 4 weeks after diagnosis
MS-MLPA (methylation-specific multiplex-ligation-dependent probe amplification)	Use of the quantitative MS-MLPA method provides detailed information about deletions, rare duplications, and possibly UPD	up to 4 weeks after diagnosis

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 28, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 7, 2019

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: deletion; FISH; M-PCR; MLPA; uniparental disomy; imprinting mutation
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Mental Disorders
• Other Study ID Numbers: B-ER-102-155-t