Microduplication and triplication of 22q11.2: a highly variable syndrome.
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.
Yobb
Twila M
TM
Department of Biological Sciences, University of Alberta, Edmonton, Canada.
Somerville
Martin J
MJ
Willatt
Lionel
L
Firth
Helen V
HV
Harrison
Karen
K
MacKenzie
Jennifer
J
Gallo
Natasha
N
Morrow
Bernice E
BE
Shaffer
Lisa G
LG
Babcock
Melanie
M
Chernos
Judy
J
Bernier
Francois
F
Sprysak
Kathy
K
Christiansen
Jesse
J
Haase
Shelagh
S
Elyas
Basil
B
Lilley
Margaret
M
Bamforth
Steven
S
McDermid
Heather E
HE
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