title: Multiplex ligation-dependent probe amplification (MLPA): a reliable alternative for fetal chromosome analysis?
abstract: OBJECTIVE
  To determine whether molecular karyotyping using multiple ligation probe amplification (MLPA) is a reliable alternative for quick and accurate diagnosis of fetal chromosomal abnormalities.
  
  
  METHODS
  MLPA, using specialised probe sets designed to detect aneuploidy, major chromosomal rearrangements and recognised microdeletion syndromes, was used to analyse chorionic villi or amniocytes left after traditional karyotyping of 476 fetuses for clinical indications.
  
  
  RESULTS
  An abnormal result was obtained in 190 cases, including 124 trisomies, 21 sex chromosome anomalies, 14 triploidies, and 31 rearrangements or mosaics. All trisomies were detected by all three techniques, but triploidies were only detected by karyotyping and QF-PCR. In 19 of the 31 cases of rearrangements or mosaicism there was an uncertain or high risk of adverse outcome. Traditional karyotyping detected 13 of the 19 pathogenic rearrangements, MLPA detected 18, and QF-PCR did not detect any.
  
  
  CONCLUSIONS
  MLPA, using specialized probe sets, detects more chromosomal rearrangements, conferring significant risk of adverse outcome than karyotyping. A combination of qfPCR and MLPA could be a good, rapid alternative to current practice. In the future, used in conjunction with non-invasive prenatal diagnosis based on cell free fetal DNA it might provide a rapid and efficient approach to fetal karyotyping.
authors.affiliation: University College London Institute of Child Health and Fetal Medicine Unit, UCLH NHS Foundation Trust, London, UK. l.chitty@ich.ucl.ac.uk
authors.forename: Lyn S
authors.initials: LS
authors.lastname: Chitty
authors.forename: James
authors.initials: J
authors.lastname: Kistler
authors.forename: Ranjit
authors.initials: R
authors.lastname: Akolekar
authors.forename: Stuart
authors.initials: S
authors.lastname: Liddle
authors.forename: Kypros
authors.initials: K
authors.lastname: Nicolaides
authors.forename: Lisa
authors.initials: L
authors.lastname: Levett
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D005820:Genetic Testing / Q000379:methods / Q000592:standards; D006801:Humans; D007621:Karyotyping; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods* / Q000592:standards; D015203:Reproducibility of Results