title: Microduplication 22q11.2, an emerging syndrome: clinical, cytogenetic, and molecular analysis of thirteen patients.
abstract: Chromosome 22, particularly band 22q11.2, is predisposed to rearrangements due to misalignments of low-copy repeats (LCRs). DiGeorge/velocardiofacial syndrome (DG/VCFS) is a common disorder resulting from microdeletion within the same band. Although both deletion and duplication are expected to occur in equal proportions as reciprocal events caused by LCR-mediated rearrangements, very few microduplications have been identified. We have identified 13 cases of microduplication 22q11.2, primarily by interphase fluorescence in situ hybridization (FISH). The size of the duplications, determined by FISH probes from bacterial artificial chromosomes and P(1) artificial chromosomes, range from 3-4 Mb to 6 Mb, and the exchange points seem to involve an LCR. Molecular analysis based on 15 short tandem repeats confirmed the size of the duplications and indicated that at least 1 of 15 loci has three alleles present. The patients' phenotypes ranged from mild to severe, sharing a tendency for velopharyngeal insufficiency with DG/VCFS but having other distinctive characteristics, as well. Although the present series of patients was ascertained because of some overlapping features with DG/VCF syndromes, the microduplication of 22q11.2 appears to be a new syndrome.
authors.affiliation: Department of Medical Genetics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Regina E
authors.initials: RE
authors.lastname: Ensenauer
authors.forename: Adewale
authors.initials: A
authors.lastname: Adeyinka
authors.forename: Heather C
authors.initials: HC
authors.lastname: Flynn
authors.forename: Virginia V
authors.initials: VV
authors.lastname: Michels
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: D Brian
authors.initials: DB
authors.lastname: Dawson
authors.forename: Erik C
authors.initials: EC
authors.lastname: Thorland
authors.forename: Cindy Pham
authors.initials: CP
authors.lastname: Lorentz
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Goldstein
authors.forename: Marie T
authors.initials: MT
authors.lastname: McDonald
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Smith
authors.forename: Elba
authors.initials: E
authors.lastname: Simon-Fayard
authors.forename: Alan A
authors.initials: AA
authors.lastname: Alexander
authors.forename: Anita S
authors.initials: AS
authors.lastname: Kulharya
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Robin D
authors.initials: RD
authors.lastname: Clark
authors.forename: Syed M
authors.initials: SM
authors.lastname: Jalal
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D020732:Cytogenetic Analysis; D005260:Female; D020440:Gene Duplication; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007399:Interphase; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D013577:Syndrome