Get access

Independent de novo 22q11.2 deletions in first cousins with DiGeorge/velocardiofacial syndrome

Authors

  • Sulagna C. Saitta,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Pennsylvania
    2. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Stacy E. Harris,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Pennsylvania
    Search for more papers by this author
  • Donna M. McDonald-McGinn,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Pennsylvania
    2. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Beverly S. Emanuel,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Pennsylvania
    2. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Melissa K. Tonnesen,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Pennsylvania
    Search for more papers by this author
  • Elaine H. Zackai,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Pennsylvania
    2. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    3. Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Suzanne C. Seitz,

    1. Genetics and IVF Institute, Fairfax, Virginia
    Search for more papers by this author
  • Deborah A. Driscoll

    Corresponding author
    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Pennsylvania
    2. Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • Division of Human Genetics and Molecular Biology, Abramson Research Center, Room 1002, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104.
    Search for more papers by this author

Abstract

Deletions of chromosome 22q11.2 are found in the vast majority of patients with DiGeorge/velocardiofacial syndrome (DGS/VCFS). This most frequent microdeletion syndrome is estimated to occur in 1 in 4,000 live births. The majority of deletions are de novo, with 10% or less inherited from an affected parent. Here, we report two separate families with recurrence of a 22q11.2 deletion in first cousins. In each family, unaffected siblings (brother and sister) had an affected child. Fluorescence in situ hybridization (FISH) studies of the parents of each affected child were normal and hence, relatives were not considered at an increased risk for recurrence in another pregnancy. We used highly polymorphic microsatellite repeat markers from within 22q11.2 to determine the parental origin of each cousin's deletion and to assess whether parental germline mosaicism for the 22q11.2 deletion might be a factor in these cases. This analysis confirmed that in each case, the deletion occurred on a chromosome 22 derived from unrelated parents, consistent with independent de novo deletion events. Thus, we concluded that germline mosaicism as the underlying mechanism for affected cousins in these families was unlikely. Our findings underscore the high frequency with which the 22q11.2 deletion occurs in the general population and demonstrate the important role that PCR-based parental origin determination can have in recurrence risk counselling. Furthermore, relatives of affected individuals may benefit from genetic counselling and consider prenatal testing for the 22q11.2 deletion in future pregnancies, despite a low recurrence risk. © 2003 Wiley-Liss, Inc.

Ancillary