Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes.
OBJECTIVE
Genomic rearrangements of chromosome 22q11.2, including the microdeletion associated with DiGeorge/velocardiofacial syndrome, are mediated by nonallelic homologous recombination between region-specific low-copy repeats. To date, only a small number of patients with 22q11.2 microduplication have been identified.


METHODS
We report the identification by array-comparative genomic hybridization of 14 individuals from eight families who harbor microduplications within the 22q11.2 region.


RESULTS
We have now observed a variety of microduplications, including the typical common approximately 3-Mb microduplication, approximately 1.5-Mb nested duplication, and smaller microduplications within and distal to the DiGeorge/velocardiofacial syndrome region, consistent with nonallelic homologous recombination using distinct low-copy repeats in the 22q11.2 DiGeorge/velocardiofacial syndrome region. These microduplications likely represent the predicted reciprocal rearrangements to the microdeletions characterized in the 22q11.2 region. The phenotypes seen in these individuals are generally mild and highly variable; familial transmission is frequently observed.


CONCLUSIONS
These findings highlight the unbiased ability of array-comparative genomic hybridization to identify genomic imbalances and further define the molecular etiology and clinical phenotypes seen in microduplication 22q11.2 syndrome. Our findings also further support that the 22q11.2 region is highly dynamic with frequent rearrangements using alternative low-copy repeats as recombination substrates.
Ou
Zhishuo
Z
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Berg
Jonathan S
JS
Yonath
Hagith
H
Enciso
Victoria B
VB
Miller
David T
DT
Picker
Jonathan
J
Lenzi
Tiffanee
T
Keegan
Catherine E
CE
Sutton
Vernon R
VR
Belmont
John
J
Chinault
A Craig
AC
Lupski
James R
JR
Cheung
Sau Wai
SW
Roeder
Elizabeth
E
Patel
Ankita
A
D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D040582:Inheritance Patterns / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype