IntroductionPrader-Willi syndrome (PWS) is characterised byobesity, short stature, small hands and feet, neonatalhypotonia with difficulty in feeding at birth,hypogonadism and eye problems. At about two years ofage the feeding difficulties with poor suck are graduallyreplaced by hyperphagia and obsession with food,leading to the obesity. In addition to developmentaldelay which is manifested by short stature, small handsand feet, growth hormone deficiency andhypogenitalism/hypogonadism, there are alsobehavioural characteristics including learningdisabilities, temper tantrums, aggression, repetitivespeech, obsessive compulsive behaviour, sleep disorderand skin picking (Cassidy and Driscoll, 2009). Thisdisparate collection of symptoms led Holm et al (1993)to define the major and minor characteristics whichallowed a clinical diagnosis of this the most commongenetic form of obesity. Consensus diagnostic criteriawere defined and weighted scores in which the majorcriteria were awarded one point and the minor criteriahalf a point calculated. A score of 8 or more is clinicallydiagnostic for PWS.The majority of people with PWS have a paternallyderived deletion of approximately 5-7Mb in 15q11-q13,others have maternal disomy of chromosome 15(UPD15mat) and a minority have a defect of theimprinting centre located in exon 1 of the SNRPN genewhich leads to a maternal imprint on the paternallyderived chromosome. Any of these abnormalities willresult in loss of the paternal contribution to the Prader-Willi syndrome critical region (PWSCR), demonstratedby loss of a paternally derived unmethylated band at theimprinting centre and a lack of expression of the SNRPNgene. Although these do not differentiate between thedifferent genetic types of PWS they are diagnostic forthe syndrome (Cassidy and Driscoll, 2009; Ramsden etal, 2010; Zeschnigk et al, 1997).Within 15q11-q13 the complex imprintedSNURF/SNRPN gene hosts several untranslated snoRNAgenes located within intronic sequences. The finding ofa microdeletion involving SNORD116 in a boy with PWSled to the identification of this snoRNA as the candidategene for the syndrome (Sahoo et al, 2008).In the course of a large study of PWS in the UK(Whittington et al, 2001; Soni et al, 2007) three peoplewere identified who fulfilled the criteria for a clinicaldiagnosis of the syndrome but not the geneticlaboratory diagnostic criteria.The Affymetrix Cytogenetics Whole-Genome 2.7M arraywhile providing high resolution whole genome coveragereliably detects changes in copy number. Deletionsand/or duplications present in all three participants ifinvolved in annotated genes could potentiallycontribute to the Prader-Willi-like phenotype.Candidate genes can subsequently be evaluated toestimate their transcription levels and compared withthose shown by people with PWS and with unaffectedindividuals
