Methods for routine diagnosis of genomic rearrangements: multiplex PCR-based methods and future perspectives

摘要

Germline and somatic genomic rearrangement play a relevant role in the pathogenesis ofngenetic disorders, and their identification is a fundamental task in molecular diagnosis.nHowever, screening for structural genomic abnormalities is often not included in routinenmutational analyses and consequently the proportion of rearrangements playing a pathogenicnrole in several genetic disorders is likely to be underestimated. A wide range of molecularntechniques for the detection of large genomic rearrangements has been developed: somenmethods have the power to screen the whole genome, others are designed to analyze one ornfew loci that are known to be involved in a specific disease; some may detect balancednrearrangements, while others only unbalanced rearrangements; some are suitable forndetection of germline abnormalities, yet others also detect somatic abnormalities. This reviewnprovides a brief summary of principles, applications and limitations of the methods availablenfor the screening of genomic rearrangements, focusing on multiplex PCR-based protocols thatnare currently employed in routine detection of extended germline genomic deletions ornduplications. Future developments based on microarray platforms and high-throughputnsequencing are also discussed.