De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndromeReportar como inadecuado




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Genome Medicine

, 5:11

6. Ethical, legal and social issues

Abstract

BackgroundMolecular 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.

MethodsWe used whole-genome and whole-exome sequencing to interrogate the genomes of four subjects with an undiagnosed syndrome.

ResultsUsing 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.

ConclusionWe have identified truncating mutations in ASXL3 as the likely cause of a novel syndrome with phenotypic overlap with Bohring-Opitz syndrome.

List of abbreviationsBCM-HGSCBaylor College of Medicine Human Genome Sequencing Center

BOSBohring-Opitz Syndrome

BWABurrows-Wheeler Aligner

CdLSCornelia de Lange Syndrome

miRNAmicroRNA

MPIMGMax Planck Institut für molekulare Genetik

NMDnonsense-mediated decay

qPCRquantitative polymerase chain reaction

SNVsingle-nucleotide variant.

Electronic supplementary materialThe online version of this article doi:10.1186-gm415 contains supplementary material, which is available to authorized users.

Richard A Gibbs and H Hilger Ropers contributed equally to this work.

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Autor: Matthew N Bainbridge - Hao Hu - Donna M Muzny - Luciana Musante - James R Lupski - Brett H Graham - Wei Chen - Karen W

Fuente: https://link.springer.com/







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