Main Article Content
Background: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are well-characterised conditions in which the phenotypes and genes responsible are distinct, but they share a common genetic mechanism. PWS is due to a lack of paternally-expressed genes located to human chromosome region 15q11-q13, and AS is due to a lack of maternally-expressed genes located to the same region. There are a variety of testing strategies available to determine if a patient has either of these syndromes.
Methods and results: In this study, we tested two of the methods used in clinical laboratories to confirm a diagnosis of PWS and AS: methylation sensitive PCR (MS-PCR) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). Thirty samples which had previously been tested for either PWS or AS by MS-PCR were blinded and tested prospectively by MS-MLPA.
Conclusions: Both tests showed complete concordance with respect to confirming a clinical diagnosis. Of the three principal mutation mechanisms underpinning PWS/AS, MS-PCR cannot resolve any of them while MS-MLPA can detect deletion events; neither can differentiate between uniparental disomy or point mutations in the imprinting centre. Both techniques provide an accurate confirmation of a clinical diagnosis with the possibility of a quick turnaround time of approximately two days. Therefore, either technique would be of benefit in a routine diagnostic laboratory.
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
 Gunay-Aygun M, Schwartz S, Heeger MS, et al. The Changing Purpose of Prader-Willi Syndrome Clinical Diagnostic Criteria and Proposed Revised Criteria. Pediatics 2001;108: e92.
 Bittel DC, Butler MG. Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev. Mol. Med. 2005;14:DOI: 10.1017/S1462399405009531.
 Zhang K, Liu S, et al. Clinical Application of an Innovative Multiplex-Fluorescent-Labeled STRs Assay for Prader-Willi Syndrome and Angelman Syndrome. PLOS ONE 2016;DOI:10.1371/journal.pone.0147824.
 Marijcke WM, Craig EE, Bolton PF. Autistic spectrum disorders in Prader-Willi and Angelman syndromes: a systematic review. Psychiatric Genetics 2005; 15: 243-254.
 Bird LM. Angelman syndrome: review of clinical and molecular aspects. The Application of Clinical Genetics 2014; 7: 93-104.
 Buiting K. Prader-Willi Syndrome and Angelman Syndrome. Am J of Med Genet Part C Semin Med Genet 2010; 154C: 365-376.
 Sahoo T, Peters SU, Madduri NS, et al. Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations. J Med Genet 2006; 43: 512-516.
 Ramsden SC, Clayton-Smith J, Birch R, et al. Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes. BMC Medical Genetics 2010; 11: 70.
 Kim S, Miller JL, Kuipers PJ, et al. Unique and atypical deletions in Prader-Willi syndrome reveal distinct phenotypes. European Journal of Human Genetics 2012; 20:283-290.
 Hartley SL, MacLean WE, Butler MG, et al. Maladaptive Behaviours and Risk Factors Among the Genetic Subtypes of Prader-Willi Syndrome. Am J Med Genet A 2005; 136: 140-145.
 Butler MG, Bittel DC, Kibiryeva N, et al. An Interstitial 15q11q14 Deletion: Expanded Prader-Willi Syndrome Phenotype. Am J Med Genet A 2010; 152A: 404-408.
 Butler MG. Prader-Willi Syndrome: Obesity due to Genomic Imprinting. Current Genomics 2011; 12:204-215.
 Angulo MA, Butler MG, Cataletto ME. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J Endocrinol Invest 2015; 38: 1249-1263.
 Cassidy SB, Driscoll DJ. Prader-Willi syndrome. European Journal of Human of Human Genetics 2009; 17: 3-13.
 Cassidy MD, Schwartz S, Miller JL, et al. Prader-Willi syndrome. Genetics in Medicine 2012; 14: 10-26.
 Schulze A, Hansen C, Skakkebaek NE, et al. Exclusion of SNRPN as a major determinant of Prader-Willi syndrome by a translocation breakpoint. Nature Genetics 1996; 12: 452-454.
 Wirth J, Back E, Huettenhofer A, et al. A translocation breakpoint cluster disrupts the newly defined 3’ end of the SNURF-SNRPN transcription until on chromosome 15. Human Molecular Genetics 2001; 10: 201-210.
 Duker AL, Ballif BC, Bawle EV, et al. Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader-Willi syndrome. European Journal of Human Genetics 2010; 18: 1196-1201.
 Bieth E, Eddiry S, Gaston V, et al. Highly restricted deletion of the SNORD116 region is implicated in Prader-Willi Syndrome. European Journal of Human Genetics 2015; 23: 252-255.
 Nicholls RD, Shinji S, Horshemke B. Imprinting in Prader-Willi and Angelman syndromes. Trends in Genetics 1998; 14: 194-200.
 Chamberlain SJ, Brannan CI. The Prader-Willi Syndrome Imprinting Centre Activates the Paternally Expressed Murine Ube3a Antisense Transcript but Represses Paternal Ube3a. Genomics 2001; 73: 316-322.
 Dindot SV, Antalffy BA, Bhattacharjee MB, et al. The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Human Mol Genet 2008; 17: 111-118.
 Askree SH, Hjelm LN, Pervaiz MA, et al. Allelic Dropout Can Cause False-Positive Results for Prader-Willi and Angelman Syndrome Testing. The Journal of Molecular Diagnostics 2011;13:108-112.
 Procter M, Chou L, Tang W, et al. Molecular Diagnosis of Prader-Willi and Angelman Syndromes by Methylation-Specific Melting Analysis and Methylation-Specific Multiplex Ligation-Dependent Probe Amplification. Clinical Chemistry 2006; 52: 1276-1283.
 Smith A, Hung D. The dilemma of diagnostic testing for Prader-Willi syndrome. Transl Pediatr 2016. doi: 10.21037/tp.2016.07.04.
 Buiting K, Gross S, Lich C, et al. Epimutations in Prader-Willi and Angelman Syndromes: A Molecular Study of 136 Patients with an Imprinting Defect. Am J Hum Genet 2003; 72: 571-577.
 Butler MG, Bittel DC, Kibiryeva N, et al. Behavioural Differences Among Subjects With Prader-Willi Syndrome and Type I or Type II Deletion and Maternal Disomy. Pediatrics 2004; 113: 565-573.
 Dykens EM, Roof E. Behaviour in Prader-Willi syndrome: relationship to genetic subtypes and age. Journal of Child Psychology and Psychiatry 2008; 49: 1001-1008.
 Milner KM, Craig EE, Thompson RJ, et al. Prader-Willi syndrome: intellectual abilities and behavioural features by genetic subtypes. Journal of Child Psychology and Psychiatry 2005; 46: 1089-1096.
 Varela MC, Kok F, Setian N, et al. Impact of molecular mechanisms, including deletion size, on Prader-Willi syndrome phenotype: study of 75 patients. Clin Genet 2005; 67: 47-52.
 Varela MC, Kok F, Otto PA, et al. Phenotypic variability in Angelman syndrome: comparison among different deletion classes and between deletion and UPD subjects. European Journal of Human Genetics 2004; 12: 987-992.
 Gillessen-Kaesbach G, Gross S, Kaya-Westerloh S, et al. DNA methylation based testing of 450 patients suspected of having Prader-Willi syndrome. J Med Genet 1995; 32: 88-92.
 Kosaki K, McGinniss MJ, Veraksa AN, et al. Prader-Willi and Angelman Syndromes: Diagnosis With a Bisulfite-Treated Methylation-Specific PCR Method. American Journal of Medical Genetics 1997; 73: 303-313.
 Monaghan KG, Van Dyke DL. (2006). Laboratory testing for prader-willi syndrome. In Management of Prader-Willi Syndrome: Third Edition. (pp. 74-93). Springer New York. DOI: 10.1007/978-0-387-33536-0_4.
 Gardner RJ, Sutherland GR. Shaffer, LG. (2012) Chromosome abnormalities and genetic counseling ,Oxford ; Oxford University Press.