PMID- 23000084
OWN - NLM
STAT- MEDLINE
DCOM- 20130614
LR  - 20220311
IS  - 1472-6491 (Electronic)
IS  - 1472-6483 (Linking)
VI  - 25
IP  - 5
DP  - 2012 Nov
TI  - Circulating trophoblastic cells provide genetic diagnosis in 63 fetuses at risk 
      for cystic fibrosis or spinal muscular atrophy.
PG  - 508-20
LID - S1472-6483(12)00524-X [pii]
LID - 10.1016/j.rbmo.2012.08.002 [doi]
AB  - This study sought to determine whether a reliable non-invasive prenatal diagnosis 
      (NI-PND) of cystic fibrosis (CF) or spinal muscular atrophy (SMA) can be achieved 
      through analysis of circulating fetal trophoblastic cells (CFTC). The kinetics of 
      CFTC circulation were also studied. CFTC were isolated by isolation by size of 
      epithelial tumour/trophoblastic cells at 9-11 weeks of gestation, before 
      chorionic villus sampling (CVS), from the blood of 63 pregnant women at 25% risk 
      for having a child affected by either CF (n=32) or SMA (n=31). Collected cells 
      were laser-microdissected, short tandem repeat-genotyped to determine fetal 
      origin and blindly assessed for mutation analysis. CFTC were independently 
      analysed weekly (4-12 weeks of gestation) in 14 women who achieved pregnancy 
      following IVF. Diagnostic results were compared with those obtained by CVS. All 
      seven CF and seven SMA pregnancies carrying an affected fetus were correctly 
      identified as well as non-affected pregnancies. CFTC provided 100% diagnostic 
      sensitivity (95% CI 76.8-100%) and specificity (95% CI 92.7-100%) in these 63 
      consecutive pregnancies at risk for CF or SMA. CFTC were found to circulate from 
      5 weeks of gestation and can be used to develop an early and reliable approach 
      for NI-PND. We sought to determine whether a reliable non-invasive prenatal 
      diagnosis (NI-PND) of two rare genetic diseases - cystic fibrosis (CF) and spinal 
      muscular atrophy (SMA) - can be achieved through analysis of circulating fetal 
      trophoblastic cells (CFTC) in blood of pregnant women. We also studied the time 
      of appearance and circulation of CFTC in maternal blood. CFTC were isolated from 
      maternal blood by isolation by size of epithelial tumour/trophoblastic cells 
      (ISET; an approach for cell isolation from blood) at 9-11 weeks of gestation 
      before chorionic villus sampling (CVS) from the blood of 63 pregnant women at 25% 
      risk for having a child affected by either CF (n=32) or SMA (n=31). Collected 
      cells were analysed by genetic test to determine fetal origin and blindly 
      assessed for mutation analysis. We independently analysed CFTC in maternal blood 
      samples taken weekly (4-12 weeks of gestation) from 14 women who achieved 
      pregnancy following IVF. Diagnostic results were compared with those obtained by 
      CVS. All seven CF and seven SMA pregnancies carrying an affected fetus were 
      correctly identified as well as non-affected pregnancies. CFTC provided 100% 
      diagnostic sensitivity and specificity in these 63 consecutive pregnancies at 
      risk for CF or SMA. CFTC were found to circulate from 5 weeks of gestation and 
      can be used to develop an early and reliable approach for NI-PND.
CI  - Copyright (c) 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All 
      rights reserved.
FAU - Mouawia, Hussein
AU  - Mouawia H
AD  - Unite INSERM 807, Universite Paris Descartes, Paris, France.
FAU - Saker, Ali
AU  - Saker A
FAU - Jais, Jean-Philippe
AU  - Jais JP
FAU - Benachi, Alexandra
AU  - Benachi A
FAU - Bussieres, Laurence
AU  - Bussieres L
FAU - Lacour, Bernard
AU  - Lacour B
FAU - Bonnefont, Jean-Paul
AU  - Bonnefont JP
FAU - Frydman, Rene
AU  - Frydman R
FAU - Simpson, Joe Leigh
AU  - Simpson JL
FAU - Paterlini-Brechot, Patrizia
AU  - Paterlini-Brechot P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20120831
PL  - Netherlands
TA  - Reprod Biomed Online
JT  - Reproductive biomedicine online
JID - 101122473
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Cystic Fibrosis/*diagnosis/genetics
MH  - Female
MH  - Genetic Markers
MH  - Genotype
MH  - Gestational Age
MH  - Heterozygote
MH  - Humans
MH  - Muscular Atrophy, Spinal/*diagnosis/genetics
MH  - Polymerase Chain Reaction
MH  - Pregnancy
MH  - Prenatal Diagnosis/*methods
MH  - Sensitivity and Specificity
MH  - Trophoblasts/*cytology
EDAT- 2012/09/25 06:00
MHDA- 2013/06/15 06:00
CRDT- 2012/09/25 06:00
PHST- 2012/03/14 00:00 [received]
PHST- 2012/08/16 00:00 [revised]
PHST- 2012/08/16 00:00 [accepted]
PHST- 2012/09/25 06:00 [entrez]
PHST- 2012/09/25 06:00 [pubmed]
PHST- 2013/06/15 06:00 [medline]
AID - S1472-6483(12)00524-X [pii]
AID - 10.1016/j.rbmo.2012.08.002 [doi]
PST - ppublish
SO  - Reprod Biomed Online. 2012 Nov;25(5):508-20. doi: 10.1016/j.rbmo.2012.08.002. 
      Epub 2012 Aug 31.