PRADER-WILLI SYNDROME & ANGELMAN SYNDROME
Prader-Willi (PWS OMIM 176270) and Angelman (AS OMIM 105830) syndromes are clinically distinct syndromes both of which are caused by abnormalities involving an imprinted domain within chromosome region 15q11-q13.
PWS is characterised by feeding problems in infancy usually progressing to hyperphagia and obesity in adolescence. Other characteristic features of this syndrome include short stature, hypogonadism, and mild to moderate mental retardation. 75-80% of PWS patients have a paternal deletion of 15q11-q13, 20-25% have maternal uniparental disomy (UPD) of chromosome 15, 10-15% have an imprinting centre deletion and ~1% have an imprinting defect (with an imprinting centre deletion excluded). The recurrence risk to the parents of an affected child is low except if the patient has an imprinting centre deletion which can show up to 50% recurrence if present in the father.
AS is characterised by severe mental retardation, absence of speech, ataxic gait, seizures, as well as inappropriate bouts of laughter. 70-75% of AS patients have a paternal deletion of 15q11-q13, 3-7% have paternal uniparental disomy (UPD) of chromosome 15, 10-15% have an imprinting centre deletion, 2-3% have an imprinting defect (with an imprinting centre deletion excluded), ~10% have a UBE3A mutation and ~10% have no identifiable molecular abnormality. There is a recurrence risk to the parents of an affected child which is dependent on the genetic defect: if the patient has an imprinting centre deletion recurrence risk is up to 50% if present in the father; if the patient has a UBE3A mutation, recurrence risk is 50% if present in the mother; if there is no identifiable molecular abnormality, the recurrence risk is unknown.
Testing at WRGL
Methylation-specific multiplex-dependent probe amplification (MS-MLPA) is used to detect aberrant methylation and to detect deletions at 15q11-q13. MS-MLPA analysis is performed using a commercially available kit (ME028) from MRC Holland (www.mrc-holland.com) followed by analysis on a 3130 Genetic Analyser. Data is analysed using GeneMarker software (www.softgenetics.com).
Cost, Sample Requirements & Turnaround Times
|Prader-Willi and Angelman syndrome MS-MLPA||$406||Adults: 4 ml in EDTA (purple top)
Children: 1-2 ml in EDTA (purple top)
For newborns and very young babies supply 1 ml EDTA (purple top)
|urgent 2 days
routine 1 week
|FISH analysis||$508||4 ml of whole blood in a lithium heparin (LH) tube (green top)||3 days|
|Uniparental disomy 15 testing||$406||4 ml of whole blood in EDTA (purple top) from each parent||1-2 weeks|
*No direct charge for the central region DHBs covered by the Crown Funding Agreement