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Genomic and clinical characteristics of microduplications in chromosome 17

Authors

  • Oleg A. Shchelochkov,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Division of Genetics, Department of Pediatrics, University of Iowa, Iowa City, Iowa
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  • S.W. Cheung,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • J.R. Lupski

    Corresponding author
    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Division of Genetics, Department of Pediatrics, University of Iowa, Iowa City, Iowa
    3. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    • Cullen Professor and Vice Chairman, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77050.
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  • How to cite this article: Shchelochkov OA, Cheung SW, Lupski JR. 2010. Genomic and clinical characteristics of microduplications in chromosome 17. Am J Med Genet Part A 152A:1101–1110.

Abstract

Genomic disorders have been increasingly recognized as a significant source of clinically relevant phenotypes largely fostered by advances in technologies for genome-wide analyses. Molecular and clinical studies of copy number variants involving chromosome 17 began with locus-specific studies of Charcot–Marie–Tooth disease type 1A (CMT1A, OMIM #118220) and hereditary neuropathy with liability to pressure palsies (HNPP, OMIM #162500), which laid the foundation for the paradigm of duplication/deletion and gene-dosage for our understanding of genomic disorders. With the clinical introduction of high-resolution array comparative genomic hybridization (aCGH) the number of recognized genomic disorders including microduplications has been increasing rapidly. A relatively high proportion of disease-associated copy number variants map to chromosome 17. This may result from its unique structural features, such as relative abundance of segmental duplications and interspersed repetitive elements, high gene content, and the presence of dosage-sensitive genes. These genomic rearrangements are mediated by diverse mechanisms including Non-Allelic Homologous Recombination (NAHR), Non-Homologous End-Joining (NHEJ), and Fork Stalling and Template Switching (FoSTeS). We provide specific examples of chromosome 17 microduplications with the emphasis on their phenotype, specific clinical features aiding in their diagnosis, and counseling. © 2010 Wiley-Liss, Inc.

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