title: Lifting the lid on unborn lethal Mendelian phenotypes through exome sequencing.
abstract: OBJECTIVE
  Mendelian phenotypes in humans vary from benign variants to lethal disorders. Embryonic lethal phenotypes that are similar to what has been known for a long time in mice have remained largely unknown because of the difficulty in arriving at a molecular diagnosis. The purpose of this study is to test whether next generation sequencing can reveal the underlying etiology of recurrent fetal loss.
  
  
  METHODS
  We hypothesized that exome sequencing combined with autozygome analysis can reveal the underlying mutation in a family in which recurrent fetal loss was likely to be autosomal recessive in origin.
  
  
  RESULTS
  A novel mutation in CHRNA1 was identified. This gene is known to cause multiple pterygium and fetal akinesia syndrome.
  
  
  CONCLUSIONS
  This is the first report of exome sequencing to identify the cause of recurrent fetal loss and reveal the diagnosis of a lethal human phenotype. Our results should inspire a systematic examination of the extent of "unborn" Mendelian phenotypes in humans using next-generation sequencing.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shamseldin
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Swaid
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000026:Abortion, Habitual / Q000175:diagnosis* / Q000209:etiology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D003241:Consanguinity; D016384:Consensus Sequence; D059472:Exome; D005260:Female; D005313:Fetal Death / Q000175:diagnosis* / Q000209:etiology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015160:Hydrops Fetalis / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: C523021:CHRNA1 protein, human; D011978:Receptors, Nicotinic