title: Global transcriptome dysregulation in second trimester fetuses with FMR1 expansions.
abstract: OBJECTIVE
  We tested the hypothesis that FMR1 expansions would result in global gene dysregulation as early as the second trimester of human fetal development.
  
  
  METHODS
  Using cell-free fetal RNA obtained from amniotic fluid supernatant and expression microarrays, we compared RNA levels in samples from fetuses with premutation or full mutation allele expansions with control samples.
  
  
  RESULTS
  We found clear signals of differential gene expression relating to a variety of cellular functions, including ubiquitination, mitochondrial function, and neuronal/synaptic architecture. Additionally, among the genes showing differential gene expression, we saw links to related diseases of intellectual disability and motor function. Finally, within the unique molecular phenotypes established for each mutation set, we saw clear signatures of mitochondrial dysfunction and disrupted neurological function. Patterns of differential gene expression were very different in male and female fetuses with premutation alleles.
  
  
  CONCLUSIONS
  These results support a model for which genetic misregulation during fetal development may set the stage for late clinical manifestations of FMR1-related disorders. © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA.
authors.forename: Lillian M
authors.initials: LM
authors.lastname: Zwemer
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Nolin
authors.affiliation: Integrated Genetics/Laboratory Corporation of America® Holdings, Westborough, MA, USA.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Okamoto
authors.affiliation: Laboratory Corporation of America® Holdings, Research Triangle Park, NC, USA.
authors.forename: Marcia
authors.initials: M
authors.lastname: Eisenberg
authors.affiliation: Department of Computer Science, Tufts University, Medford, MA, USA.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Wick
authors.affiliation: Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA.
authors.forename: Diana W
authors.identifier: http://orcid.org/0000-0001-9270-5267
authors.initials: DW
authors.lastname: Bianchi
mesh_terms: D042622:DNA Repeat Expansion; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D011247:Pregnancy; D011262:Pregnancy Trimester, Second
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human