From VACTERL-H to heterotaxy: Variable expressivity of ZIC3—related disorders

Authors

  • Brian Chung,

    1. The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    2. Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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  • Lisa G. Shaffer,

    1. Signature Genomic Laboratories, Spokane, Washington, District of Columbia
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  • Sarah Keating,

    1. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Joan Johnson,

    1. Department of Obstetrics and Gynecology, Maternal Fetal Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Bret Casey,

    1. Children's and Women's Health Centre, Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia, Canada
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  • David Chitayat

    Corresponding author
    1. The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    2. Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    • The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Genecology, The Ontario Power Generation Building, 700 University Avenue, Room 3292, Toronto, Ontario, Canada M5G 1Z5.
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  • How to Cite this Article: Chung B, Shaffer LG, Keating S, Johnson J, Casey B, Chitayat D. 2011. From VACTERL-H to heterotaxy: Variable expressivity of ZIC3—related disorders. Am J Med Genet Part A 155:1123–1128.

Abstract

The ZIC3 gene encodes a zinc finger protein which functions as a transcription factor in early stages of left-right body axis formation. Mutations in this X-linked gene cause a variety of clinical manifestations including heterotaxy, complex or isolated heart defect as well as other midline urogenital and hindgut malformations. We report a four generation family with X-linked heterotaxy associated with a deletion of the ZIC3 gene at Xq26.3. The index fetus of our proband showed classical features of heterotaxy while her maternal uncle and one brother had imperforate anus and her other brother had features suggestive of VACTERL-H without heterotaxy. A 1.4 Mb deletion in Xq26.3 including the ZIC3 gene was found in the fetus. Six females in the family were found to be asymptomatic carriers. Our report indicates that some of the cases with VACTERL-H syndrome may be caused by a mutation or deletion of the ZIC3 gene. © 2011 Wiley-Liss, Inc.

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