title: Diagnostic yield by supplementing prenatal metaphase karyotyping with MLPA for microdeletion syndromes and subtelomere imbalances.
abstract: OBJECTIVE
  The aim of the study was to retrospectively assess the relevance of using multiplex ligation-dependent probe amplification (MLPA) for detection of selected microdeletion syndromes (22q11, Prader-Willi/Angelman, Miller-Dieker, Smith-Magenis, 1p-, Williams), the reciprocal microduplication syndromes and imbalance at the subtelomere regions of chromosomes in a routine prenatal setting.
  
  
  METHODS
  A total of 530 prenatal samples were analysed by commercial MLPA kits (SALSA P064, P036 and P069) in addition to rapid aneuploidy testing and G-band karyotyping.
  
  
  RESULTS
  Among the prenatal samples with a normal metaphase karyotype, nine submicroscopic imbalances were detected: seven 22q11 deletions (Velocardiofacial/DiGeorge syndrome), one 15q11 deletion (Prader-Willi syndrome) and one terminal deletion of the short arm of chromosome 4 (Wolf-Hirschhorn syndrome). All imbalances were found in amniocentesis (AC) taken due to fetal structural malformation and/or other ultrasound scan (US) detected abnormality. The diagnostic yield was 4.1% in the subgroup with structural malformation and 1.6% in the subgroup with other US abnormality.
  
  
  CONCLUSIONS
  The data set substantiates that additional MLPA analyses for selected microdeletions and subtelomere imbalances are valuable in routine prenatal diagnostics, when a malformation(s) and/or other abnormalities are detected by US. In contrast, the additional MLPA analyses gave no diagnostic yield in case of increased nuchal translucency (NT).
authors.affiliation: Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Denmark. susanne.kjaergaard@rh.regionh.dk
authors.forename: S
authors.initials: S
authors.lastname: Kjaergaard
authors.forename: K
authors.initials: K
authors.lastname: Sundberg
authors.forename: F S
authors.initials: FS
authors.lastname: Jørgensen
authors.forename: M D
authors.initials: MD
authors.lastname: Rohde
authors.forename: A M
authors.initials: AM
authors.lastname: Lind
authors.forename: T
authors.initials: T
authors.lastname: Gerdes
authors.forename: A
authors.initials: A
authors.lastname: Tabor
authors.forename: M
authors.initials: M
authors.lastname: Kirchhoff
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D002871:Chromosome Banding / Q000379:methods; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D005260:Female; D005865:Gestational Age; D006801:Humans; D007621:Karyotyping / Q000379:methods; D008677:Metaphase; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011933:Reagent Kits, Diagnostic; D012189:Retrospective Studies; D016615:Telomere / Q000235:genetics*
chemical_list: D011933:Reagent Kits, Diagnostic