Get access

Pontocerebellar hypoplasia in association with de novo 19p13.11p13.12 microdeletion§

Authors

  • Natalie M. Gallant,

    1. Departments of Pediatrics and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California
    2. Mattel Children's Hospital at UCLA, Los Angeles, California
    Search for more papers by this author
  • Erin Baldwin,

    1. Departments of Pediatrics and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California
    2. Mattel Children's Hospital at UCLA, Los Angeles, California
    Search for more papers by this author
  • Noriko Salamon,

    1. Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, California
    Search for more papers by this author
  • Katrina M. Dipple,

    Corresponding author
    1. Departments of Pediatrics and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California
    2. Mattel Children's Hospital at UCLA, Los Angeles, California
    • Departments of Human Genetics and Pediatrics, 695 Charles E. Young Drive South, Gonda 5506B, Los Angeles, CA 90095-7088.
    Search for more papers by this author
  • Fabiola Quintero-Rivera

    Corresponding author
    1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
    • Department of Pathology and Laboratory Medicine, 1000 Veteran Avenue. 22–26, Los Angeles, CA.
    Search for more papers by this author

  • How to Cite this Article: Natalie M. Gallant, Erin Baldwin, Noriko Salamon, Katrina M. Dipple, Fabiola Quintero-Rivera. 2011. Pontocerebellar hypoplasia in association with de novo 19p13.11p13.12 Microdeletion. Am J Med Genet Part A 155: 2871–2878.

  • Katrina M. Dipple and Fabiola Quintero-Rivera are co-senior authors and contributed equally to this work.

  • §

    This case was presented as a poster at the American College of Medical Genetics annual meeting held in Vancouver, Canada, March 16–20, 2011, Poster #257.

Abstract

The pontocerebellar hypoplasias (PCHs) are a group of clinically variable disorders characterized by abnormally small cerebellum and brainstem, generally inherited in an autosomal recessive pattern. While PCHs have been grouped into six subtypes, clinical diagnosis is equivocal until a genetic diagnosis is established. We report a patient with PCH, intrauterine growth restriction, ventricular septal defect, rib anomalies, midgut malrotation, and facial dysmorphic features. Using SNP analysis, we identified three de novo deletions of: 1.055 Mb at 6q24.3q25.1 (148174730–149229583); 169 kb at 16p13.2 (6565411–6733934); and 2.530 Mb at 19p13.11p13.12 (13857587–16387798), which were confirmed by FISH. 19p13 deletions are rare aberrations. Of patients previously described with overlapping 19p13.12 deletions and multiple anomalies, only one presented with PCH. Deleted in both that patient and the patient reported here, is DDX39, a DEAD-box RNA helicase. DDX39 is part of the homeostatic machinery that regulates the switch of cellular proliferation and differentiation. It is highly expressed in the developing central nervous system and optic cup of Xenopus laevis. The brain abnormalities in the patient reported here were more severe than the previously reported patient, which may be due to additional deletions or undetected point mutations in the nondeleted allele. Notably, the patient reported here also has a partial deletion of RBFOX1 (A2BP1), which lies within the autism susceptibility locus on 16p13.2. Our findings suggest chromosomal microarray analysis may be useful in determining etiology of syndromic PCH. © 2011 Wiley Periodicals, Inc.

Ancillary