RT Journal Article SR Electronic T1 Molecular genetic classification in Prader-Willi syndrome: a multisite cohort study JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmedgenet-2018-105301 DO 10.1136/jmedgenet-2018-105301 A1 Merlin G Butler A1 Samantha N Hartin A1 Waheeda A Hossain A1 Ann M Manzardo A1 Virginia Kimonis A1 Elisabeth Dykens A1 June Anne Gold A1 Soo-Jeong Kim A1 Nicolette Weisensel A1 Roy Tamura A1 Jennifer L Miller A1 Daniel J Driscoll YR 2018 UL http://jmg.bmj.com/content/early/2018/05/05/jmedgenet-2018-105301.abstract AB Background Prader-Willi syndrome (PWS) is due to errors in genomic imprinting. PWS is recognised as the most common known genetic cause of life-threatening obesity. This report summarises the frequency and further characterises the PWS molecular classes and maternal age effects.Methods High-resolution microarrays, comprehensive chromosome 15 genotyping and methylation-specific multiplex ligation probe amplification were used to describe and further characterise molecular classes of maternal disomy 15 (UPD15) considering maternal age.Results We summarised genetic data from 510 individuals with PWS and 303 (60%) had the 15q11-q13 deletion; 185 (36%) with UPD15 and 22 (4%) with imprinting defects. We further characterised UPD15 findings into subclasses based on the presence (size, location) or absence of loss of heterozygosity (LOH). Additionally, significantly older mothers (mean age=32.5 years vs 27.7 years) were found in the UPD15 group (n=145) compared with the deletion subtype (n=200).Conclusions We report on molecular classes in PWS using advanced genomic technology in the largest cohort to date. LOH patterns in UPD15 may impact the risk of having a second genetic condition if the mother carries a recessive mutant allele in the isodisomic region on chromosome 15. The risk of UPD15 may also increase with maternal age.