title: Microduplication and triplication of 22q11.2: a highly variable syndrome.
abstract: 22q11.2 microduplications of a 3-Mb region surrounded by low-copy repeats should be, theoretically, as frequent as the deletions of this region; however, few microduplications have been reported. We show that the phenotype of these patients with microduplications is extremely diverse, ranging from normal to behavioral abnormalities to multiple defects, only some of which are reminiscent of the 22q11.2 deletion syndrome. This diversity will make ascertainment difficult and will necessitate a rapid-screening method. We demonstrate the utility of four different screening methods. Although all the screening techniques give unique information, the efficiency of real-time polymerase chain reaction allowed the discovery of two 22q11.2 microduplications in a series of 275 females who tested negative for fragile X syndrome, thus widening the phenotypic diversity. Ascertainment of the fragile X-negative cohort was twice that of the cohort screened for the 22q11.2 deletion. We also report the first patient with a 22q11.2 triplication and show that this patient's mother carries a 22q11.2 microduplication. We strongly recommend that other family members of patients with 22q11.2 microduplications also be tested, since we found several phenotypically normal parents who were carriers of the chromosomal abnormality.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Canada.
authors.forename: Twila M
authors.initials: TM
authors.lastname: Yobb
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Somerville
authors.forename: Lionel
authors.initials: L
authors.lastname: Willatt
authors.forename: Helen V
authors.initials: HV
authors.lastname: Firth
authors.forename: Karen
authors.initials: K
authors.lastname: Harrison
authors.forename: Jennifer
authors.initials: J
authors.lastname: MacKenzie
authors.forename: Natasha
authors.initials: N
authors.lastname: Gallo
authors.forename: Bernice E
authors.initials: BE
authors.lastname: Morrow
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Melanie
authors.initials: M
authors.lastname: Babcock
authors.forename: Judy
authors.initials: J
authors.lastname: Chernos
authors.forename: Francois
authors.initials: F
authors.lastname: Bernier
authors.forename: Kathy
authors.initials: K
authors.lastname: Sprysak
authors.forename: Jesse
authors.initials: J
authors.lastname: Christiansen
authors.forename: Shelagh
authors.initials: S
authors.lastname: Haase
authors.forename: Basil
authors.initials: B
authors.lastname: Elyas
authors.forename: Margaret
authors.initials: M
authors.lastname: Lilley
authors.forename: Steven
authors.initials: S
authors.lastname: Bamforth
authors.forename: Heather E
authors.initials: HE
authors.lastname: McDermid
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics; D020440:Gene Duplication; D014644:Genetic Variation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D013577:Syndrome