Diagnosis of Prader-Willi Syndrome and Angelman Syndrome

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Mental Disorder, Fetus Disorder

Participation Criteria
=================
Eligibility Criteria
-----------------
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:

Ages Eligible for Study
-----------------
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
M-PCR, FISH, MLPA, deletion, uniparental disomy, imprinting mutation