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Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease

Authors

  • Matthew G. Sampson,

    Corresponding author
    1. Division of Pediatric Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    • The Children's Hospital of Philadelphia, Division of Pediatric Nephrology, Room 2143 A 2nd Floor Main Building, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104.
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  • Curtis R. Coughlin II,

    1. Section of Metabolic Disease, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Paige Kaplan,

    1. Section of Metabolic Disease, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • Laura K. Conlin,

    1. Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Kevin E.C. Meyers,

    1. Division of Pediatric Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • Elaine H. Zackai,

    1. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    2. Human Molecular Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Nancy B. Spinner,

    1. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    2. Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Lawrence Copelovitch

    1. Division of Pediatric Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • How to Cite this Article: Sampson MG, Coughlin CR, Kaplan P, Conlin LK, Meyers KEC, Zackai EH, Spinner NB, Copelovitch L. 2010. Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease. Am J Med Genet Part A 152:2618–2622.

Abstract

Congenital Anomalies of the Kidney and Urinary Tract can be associated with Hirschsprung disease. We report on three children with a similar 16p11.2 microdeletion with a spectrum of clinical anomalies consisting of congenital anomalies of the kidney and urinary tract in two patients (Patients 1 and 2) and Hirschsprung disease in two patients (Patients 1 and 3), leading us to hypothesize that a gene in this region is associated with these phenotypes. Patient 1 presented with left renal agenesis, grade-IV vesicoureteral reflux, and Hirschsprung disease, Patient 2 with left renal agenesis, chronic kidney disease, chronic constipation, seizures, and developmental delay, and Patient 3 with Hirschsprung disease and normal kidneys. Genome-wide microarray analysis demonstrated overlapping microdeletions within 16p11.2. The shortest region of overlap in the three patients contained only eight genes, including the SH2 domain-containing binding protein 1 (SH2B1), an adaptor protein which has been implicated in enhancement of the tyrosine kinase activity of RET, whose role in developmental disease of the kidney and enteric enervation is well established. Our findings suggest that 16p11.2 deletions are associated with abnormalities of renal and enteric development and we hypothesize that deletion of SH2B1 may account for the observed phenotype. © 2010 Wiley-Liss, Inc.

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