Update of the EMQN/ACGS best practice guidelines for molecular analysis of Prader-Willi and Angelman syndromes

Abstract

This article is an update of the best practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes published in 2010 in BMC Medical Genetics [1]. The update takes into account developments in terms of techniques, differential diagnoses and (especially) reporting standards. It highlights the advantages and disadvantages of each method and moreover, is meant to facilitate the interpretation of the obtained results - leading to improved standardised reports.

Fig. 1

Overview of the imprinted region 15q11q13. Schematic overview of the genes located within the PWS and AS critical region on chromosome 15q11q13. Upper part - paternal allele (pat), lower part - maternal allele (mat). Blue boxes/vertical lines represent paternally expressed genes/snoRNAs; red box, maternally expressed gene; black boxes, biallelically expressed genes and arrow heads represent the orientation of transcription. IC imprinting centre, BP common breakpoint cluster region, cen centromeric, tel telomeric. Modified from Ramsden et al. [1]

Fig. 2

Testing strategies for the molecular analysis of PWS and AS using a MS-MLPA and b MS-PCR. Note that MS-PCR cannot distinguish between the different molecular causes of AS and PWS. *In case of a upd(15) both parents should be investigated to rule out cytogenetic rearrangements (e.g. Robertsonian translocations). In case of PWS or AS due to a large, heterozygous deletion the father or the mother, respectively should be investigated