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Genetic dosage compensation in a family with velo‐cardio‐facial/DiGeorge/22q11.2 deletion syndrome
Author(s) -
Alkalay Avishai A.,
Guo Tingwei,
Montagna Cristina,
Digilio M. Cristina,
Dallapiccola Bruno,
Marino Bruno,
Morrow Bernice
Publication year - 2011
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33861
Subject(s) - digeorge syndrome , genetics , gene duplication , biology , non allelic homologous recombination , homologous chromosome , chromosome , comparative genomic hybridization , fluorescence in situ hybridization , genetic recombination , recombination , gene
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.