title: De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome.
abstract: BACKGROUND
  Molecular diagnostics can resolve locus heterogeneity underlying clinical phenotypes that may otherwise be co-assigned as a specific syndrome based on shared clinical features, and can associate phenotypically diverse diseases to a single locus through allelic affinity. Here we describe an apparently novel syndrome, likely caused by de novo truncating mutations in ASXL3, which shares characteristics with Bohring-Opitz syndrome, a disease associated with de novo truncating mutations in ASXL1.
  
  
  METHODS
  We used whole-genome and whole-exome sequencing to interrogate the genomes of four subjects with an undiagnosed syndrome.
  
  
  RESULTS
  Using genome-wide sequencing, we identified heterozygous, de novo truncating mutations in ASXL3, a transcriptional repressor related to ASXL1, in four unrelated probands. We found that these probands shared similar phenotypes, including severe feeding difficulties, failure to thrive, and neurologic abnormalities with significant developmental delay. Further, they showed less phenotypic overlap with patients who had de novo truncating mutations in ASXL1.
  
  
  CONCLUSIONS
  We have identified truncating mutations in ASXL3 as the likely cause of a novel syndrome with phenotypic overlap with Bohring-Opitz syndrome.
authors: Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA ; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors: Matthew N
authors: MN
authors: Bainbridge
authors: Max-Planck-Institute for Molecular Genetics, Ihnestraße, Berlin 14195, Germany.
authors: Hao
authors: H
authors: Hu
authors: Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors: Donna M
authors: DM
authors: Muzny
authors: Max-Planck-Institute for Molecular Genetics, Ihnestraße, Berlin 14195, Germany.
authors: Luciana
authors: L
authors: Musante
authors: Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA ; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA ; Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA ; Texas Children's Hospital, 6621 Fannin, Houston, TX 77030, USA.
authors: James R
authors: JR
authors: Lupski
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA ; Texas Children's Hospital, 6621 Fannin, Houston, TX 77030, USA.
authors: Brett H
authors: BH
authors: Graham
authors: Max-Planck-Institute for Molecular Genetics, Ihnestraße, Berlin 14195, Germany ; Max-Delbrueck-Centrum für Molekulare Medizin, Robert-Rössle-Straße, Berlin, 13092, Germany.
authors: Wei
authors: W
authors: Chen
authors: AI duPont Hospital for Children, 1600 Rockland Rd, Wilmington, DE 19803, USA.
authors: Karen W
authors: KW
authors: Gripp
authors: AI duPont Hospital for Children, 1600 Rockland Rd, Wilmington, DE 19803, USA.
authors: Kim
authors: K
authors: Jenny
authors: Max-Planck-Institute for Molecular Genetics, Ihnestraße, Berlin 14195, Germany.
authors: Thomas F
authors: TF
authors: Wienker
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors: Yaping
authors: Y
authors: Yang
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA ; Texas Children's Hospital, 6621 Fannin, Houston, TX 77030, USA.
authors: V Reid
authors: VR
authors: Sutton
authors: Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA ; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors: Richard A
authors: RA
authors: Gibbs
authors: Max-Planck-Institute for Molecular Genetics, Ihnestraße, Berlin 14195, Germany.
authors: H Hilger
authors: HH
authors: Ropers
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