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Keywords {🔍}

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Topics {✒️}

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Schema {🗺️}

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         headline:De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome
         description: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. We used whole-genome and whole-exome sequencing to interrogate the genomes of four subjects with an undiagnosed syndrome. 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. We have identified truncating mutations in ASXL3 as the likely cause of a novel syndrome with phenotypic overlap with Bohring-Opitz syndrome.
         datePublished:2013-02-05T00:00:00Z
         dateModified:2013-02-05T00:00:00Z
         pageStart:1
         pageEnd:9
         license:http://creativecommons.org/licenses/by/2.0/
         sameAs:https://doi.org/10.1186/gm415
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            Truncate Mutation
            Severe Psychomotor Retardation
            ASXL3 Mutation
            Beckman Coulter Genomic
            Human Genetics
            Metabolomics
            Bioinformatics
            Medicine/Public Health
            general
            Cancer Research
            Systems Biology
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      headline:De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome
      description: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. We used whole-genome and whole-exome sequencing to interrogate the genomes of four subjects with an undiagnosed syndrome. 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. We have identified truncating mutations in ASXL3 as the likely cause of a novel syndrome with phenotypic overlap with Bohring-Opitz syndrome.
      datePublished:2013-02-05T00:00:00Z
      dateModified:2013-02-05T00:00:00Z
      pageStart:1
      pageEnd:9
      license:http://creativecommons.org/licenses/by/2.0/
      sameAs:https://doi.org/10.1186/gm415
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         Intellectual Disability
         Truncate Mutation
         Severe Psychomotor Retardation
         ASXL3 Mutation
         Beckman Coulter Genomic
         Human Genetics
         Metabolomics
         Bioinformatics
         Medicine/Public Health
         general
         Cancer Research
         Systems Biology
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            type:Organization
      name:Karen W Gripp
      affiliation:
            name:AI duPont Hospital for Children
            address:
               name:AI duPont Hospital for Children, Wilmington, USA
               type:PostalAddress
            type:Organization
      name:Kim Jenny
      affiliation:
            name:AI duPont Hospital for Children
            address:
               name:AI duPont Hospital for Children, Wilmington, USA
               type:PostalAddress
            type:Organization
      name:Thomas F Wienker
      affiliation:
            name:Max-Planck-Institute for Molecular Genetics
            address:
               name:Max-Planck-Institute for Molecular Genetics, Ihnestraße, Germany
               type:PostalAddress
            type:Organization
      name:Yaping Yang
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:V Reid Sutton
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Texas Children's Hospital
            address:
               name:Texas Children's Hospital, Houston, USA
               type:PostalAddress
            type:Organization
      name:Richard A Gibbs
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:H Hilger Ropers
      affiliation:
            name:Max-Planck-Institute for Molecular Genetics
            address:
               name:Max-Planck-Institute for Molecular Genetics, Ihnestraße, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:Max-Planck-Institute for Molecular Genetics, Ihnestraße, Germany
      name:Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Max-Planck-Institute for Molecular Genetics, Ihnestraße, Germany
      name:Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:Department of Pediatrics, Baylor College of Medicine, Houston, USA
      name:Texas Children's Hospital, Houston, USA
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:Texas Children's Hospital, Houston, USA
      name:Max-Planck-Institute for Molecular Genetics, Ihnestraße, Germany
      name:Max-Delbrueck-Centrum für Molekulare Medizin, Robert-Rössle-Straße, Berlin, Germany
      name:AI duPont Hospital for Children, Wilmington, USA
      name:AI duPont Hospital for Children, Wilmington, USA
      name:Max-Planck-Institute for Molecular Genetics, Ihnestraße, Germany
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:Texas Children's Hospital, Houston, USA
      name:Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA
      name:Max-Planck-Institute for Molecular Genetics, Ihnestraße, Germany

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