title: An association between skewed X-chromosome inactivation and abnormal outcome in mosaic trisomy 16 confined predominantly to the placenta.
abstract: Skewed X-chromosome inactivation (XCI) is frequently found in the diploid fetal tissues of individuals with mosaic trisomy that originated from a 'trisomic zygote rescue' event. This may result from a high number of trisomic cells in the embryonic cell pool at the time of XCI, which are subsequently eliminated by selection. We hypothesize that extremely skewed XCI in these mosaic cases will be associated with a poor fetal outcome due to failure to completely eliminate the trisomy from all fetal tissues. To test this hypothesis, XCI status was evaluated in 17 cases of prenatally detected trisomy 16 mosaicism. Ten of the 15 informative cases showed extreme XCI skewing ( > or = 90% inactivation of one allele) in blood or other diploid fetal tissues compared to six of the 111 controls (p < 0.001). Among these 10 'skewed' cases, 6 showed an abnormal outcome, defined as developmental abnormalities and/or intrauterine or neonatal death. In contrast, of the 5 cases without extreme skewing, none showed abnormal outcome, although outcome information was incomplete in 1 case. An additional 6 cases analyzed, involving trisomy mosaicism for other chromosomes, showed similar results. Further studies are warranted to determine if XCI status adds useful information to the prediction of pregnancy outcome in prenatally detected mosaic trisomy.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: M S
authors.initials: MS
authors.lastname: Peñaherrera
authors.forename: I J
authors.initials: IJ
authors.lastname: Barrett
authors.forename: C J
authors.initials: CJ
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Langlois
authors.forename: S L
authors.initials: SL
authors.lastname: Yong
authors.forename: S
authors.initials: S
authors.lastname: Lewis
authors.forename: H
authors.initials: H
authors.lastname: Bruyère
authors.forename: P N
authors.initials: PN
authors.lastname: Howard-Peebles
authors.forename: D K
authors.initials: DK
authors.lastname: Kalousek
authors.forename: W P
authors.initials: WP
authors.lastname: Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D002885:Chromosomes, Human, Pair 16; D004303:Dosage Compensation, Genetic; D005260:Female; D005315:Fetal Diseases / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005333:Fetus; D006801:Humans; D007231:Infant, Newborn; D009030:Mosaicism / Q000235:genetics*; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D014314:Trisomy