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A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10

Nature Genetics volume 4, pages 351–356 (1993)Cite this article

Abstract

Hirschsprung disease (HSCR) is characterized by a congenital absence of enteric ganglia along a variable length of the intestine. Although long considered to be a multifactorial disease, we have identified linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby proving monogenic inheritance in some families. A maximum two–point lod score of 3.37 (θ̂ = 0.045) was observed between HSCR and D10S176, under an incompletely penetrant dominant model. Multipoint, affecteds–only and non–parametric analyses supported this finding and localize this gene to a region of ≈7 centiMorgans, in close proximity to the locus for multiple endocrine neoplasia type 2 (MEN2). The co–occurrence of these two entities in some families might be attributable to shared pathogenetic origins.

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Author information

Author notes

  1. Susan A. Slaugenhaupt

    Present address: Molecular Neurogenetics Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts, 02129, USA

Authors and Affiliations

  1. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261, USA

    Misha Angrist, Erick Kauffman, Susan A. Slaugenhaupt, Tara Cox Matise, Erik G. Puffenberger, Sarah Shaw Washington, Daniel E. Weeks & Aravinda Chakravarti

  2. Birth Defects Unit, Royal Alexandra Hospital for Children, Camperdown, Australia

    Anthony Lipson

  3. Department of Pediatric Surgery, Westmead Hospital, Westmead, Australia

    Daniel T. Cass

  4. Pediatric Surgery Service, Department of Surgery, William Beaumont Army Medical Center, El Paso, Texas, 79920, USA

    Troy Reyna

  5. Pediatric Surgery Associates, 4415 Fifth Avenue, Webster Hall, Pittsburgh, Pennsylvania, 15213, USA

    William Sieber

  6. Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261, USA

    Aravinda Chakravarti

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Angrist, M., Kauffman, E., Slaugenhaupt, S. et al. A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10. Nat Genet 4, 351–356 (1993). https://doi.org/10.1038/ng0893-351

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