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

Avishai A. Alkalay, Tingwei Guo, Cristina Montagna, M. Cristina Digilio, Bruno Dallapiccola, Bruno Marino, Bernice Morrow

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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 3Mb 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.

Original languageEnglish (US)
Pages (from-to)548-554
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Issue number3
StatePublished - Mar 2011


  • Cytogenetic analysis
  • DiGeorge syndrome
  • Dosage compensation
  • Fluorescence
  • Genetic
  • In situ hybridization
  • Oligonucleotide array
  • Recurrence risks
  • Sequence analysis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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