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Familial Microdeletion of 17q24.3 Upstream of SOX9 Is Associated With Isolated Pierre Robin Sequence Due to Position Effect

Authors

  • Ina E. Amarillo,

    1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
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  • Katrina M. Dipple,

    1. Department of Human Genetics and Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
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  • Fabiola Quintero-Rivera M.D., FACMG

    Corresponding author
    • Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
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  • There is no conflict of interest.
  • Author contributions: I.A. helped interpreting the microarray results and wrote manuscript draft. K.D. evaluated the patient and provided clinical information. F.Q.-R. made the microarray diagnosis and wrote manuscript draft.

Clinical and Molecular Cytogenetics Laboratory, University of California Los Angeles, Los Angeles, CA 90024. E-mail: fquintero@mednet.ucla.edu

Abstract

Pierre Robin sequence (PRS) is a malformation pattern characterized by the core triad of retrognathia, glossoptosis, and cleft palate that causes difficulty in glossopharyngeal–laryngeal–vagal functions. The etiology of PRS remains largely unknown; previous reports have suggested that it is caused by intrauterine constriction or external conditions such as oligohydramnios, breech position, or abnormal uterine anatomy. Genetic causes include occurrence as a manifestation of many single gene conditions and chromosomal rearrangements. Positional effect on some loci or genes, including SOX9 has also been posited as a cause. Here, we report on an 18-month-old girl born with isolated PRS. Clinical chromosome microarray analysis (CMA) revealed a maternally inherited ∼623 kb microdeletion that is −725 kb upstream of 5′ SOX9 at chromosome locus 17q24.3. Her mother had cleft palate. This region, although devoid of any genes, is known to have a position effect on SOX9 due to elimination of highly conserved non-coding cis-regulatory elements. This report supports the evidence that deregulation of an intact SOX9 coding region is a cause of or associated with isolated PRS, and provides further evidence that CMA in the clinical setting is a powerful tool in detecting microdeletions in gene “desert” regions that have pathogenic position effect on specific genes. © 2013 Wiley Periodicals, Inc.

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