Research Article

Genetic dosage compensation in a family with velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome†

  1. Avishai A. Alkalay1,
  2. Tingwei Guo2,
  3. Cristina Montagna2,
  4. M. Cristina Digilio3,
  5. Bruno Dallapiccola3,
  6. Bruno Marino4,
  7. Bernice Morrow2,*

Article first published online: 18 FEB 2011

DOI: 10.1002/ajmg.a.33861

Issue

American Journal of Medical Genetics Part A

American Journal of Medical Genetics Part A

Volume 155, Issue 3, pages 548–554, March 2011

Additional Information

How to Cite

Alkalay, A. A., Guo, T., Montagna, C., Digilio, M. C., Dallapiccola, B., Marino, B. and Morrow, B. (2011), Genetic dosage compensation in a family with velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome. Am. J. Med. Genet., 155: 548–554. doi: 10.1002/ajmg.a.33861

Author Information

  1. 1

    Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York

  2. 2

    Department of Genetics, Albert Einstein College of Medicine, Bronx, New York

  3. 3

    Bambino Gesú Pediatric Hospital, IRCCS, Rome, Italy

  4. 4

    University La Sapienza, Pediatric Cardiology, Rome, Italy

*Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461.

  1. †

    How to Cite this Article: Alkalay AA, Guo T, Montagna C, Digilio MC, Dallapiccola B, Marino B, Morrow B. 2011. Genetic dosage compensation in a family with velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome. Am J Med Genet Part A 155: 548–554.

Publication History

  1. Issue published online: 24 FEB 2011
  2. Article first published online: 18 FEB 2011
  3. Manuscript Accepted: 23 NOV 2010
  4. Manuscript Received: 5 AUG 2010

Funded by

  • NIH. Grant Number: HL084410

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Keywords:

  • DiGeorge syndrome;
  • dosage compensation;
  • genetic;
  • oligonucleotide array;
  • sequence analysis;
  • in situ hybridization;
  • fluorescence;
  • cytogenetic analysis;
  • recurrence risks

Abstract

Cytogenetic studies of a male child carrying the 22q11.2 deletion common in patients with velo-cardio-facial/DiGeorge syndrome showed an unexpected rearrangement of the 22q11.2 region in his normal appearing mother. The mother carried a 3 Mb deletion on one copy and a reciprocal, similar sized duplication on the other copy of chromosome 22q11.2 as shown by fluorescence in situ hybridization and array comparative genome hybridization analyses. The most parsimonious mechanism for the rearrangement is a mitotic non-allelic homologous recombination event in a cell in the early embryo soon after fertilization. The normal phenotype of the mother can be explained by the theory of genetic dosage compensation. This is the second documented case of such an event for this or any genomic disorder. This finding helps to reinforce this phenomenon in a human model, and has significant implications for recurrence risks for the dose-compensated mother. © 2011 Wiley-Liss, Inc.

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