title: Noninvasive prenatal diagnosis of Huntington disease: detection of the paternally inherited expanded CAG repeat in maternal plasma.
abstract: OBJECTIVE
  With a shift towards noninvasive testing, we have explored and validated the use of noninvasive prenatal diagnosis (NIPD) for Huntington disease (HD).
  
  
  METHODS
  Fifteen couples have been included, assessing a total of n = 20 pregnancies. Fetal paternally inherited CAG repeat length was determined in total cell-free DNA from maternal plasma using a direct approach by PCR and subsequent fragment analysis.
  
  
  RESULTS
  All fetal HD (n = 7) and intermediate (n = 3) CAG repeats could be detected in maternal plasma. Detection of repeats in the normal range (n = 10) was successful in n = 5 cases where the paternal repeat size could be distinguished from maternal repeat patterns after fragment analysis. In all other cases (n = 5), the paternal peaks coincided with the maternal peak pattern. All NIPD results were concordant with results from routine diagnostics on fetal genomic DNA from chorionic villi.
  
  
  CONCLUSIONS
  In this validation study, we demonstrated that all fetuses at risk for HD could be identified noninvasively in maternal plasma. Additionally, we have confirmed results from previously described case reports that NIPD for HD can be performed using a direct approach by PCR. For future diagnostics, parental CAG profiles can be used to predict the success rate for NIPD prior to testing.
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jessica M E
authors.initials: JM
authors.lastname: van den Oever
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Emilia K
authors.initials: EK
authors.lastname: Bijlsma
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ilse
authors.initials: I
authors.lastname: Feenstra
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: Muntjewerff
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Inge B
authors.initials: IB
authors.lastname: Mathijssen
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Egbert
authors.initials: E
authors.lastname: Bakker
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martine J
authors.initials: MJ
authors.lastname: van Belzen
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Elles M J
authors.initials: EM
authors.lastname: Boon
mesh_terms: D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D062145:Maternal Serum Screening Tests; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011247:Pregnancy
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins