TY - JOUR
T1 - Microduplication and triplication of 22q11.2
T2 - A highly variable syndrome
AU - Yobb, Twila M.
AU - Somerville, Martin J.
AU - Willatt, Lionel
AU - Firth, Helen V.
AU - Harrison, Karen
AU - MacKenzie, Jennifer
AU - Gallo, Natasha
AU - Morrow, Bernice E.
AU - Shaffer, Lisa G.
AU - Babcock, Melanie
AU - Chernos, Judy
AU - Bernier, Francois
AU - Sprysak, Kathy
AU - Christiansen, Jesse
AU - Haase, Shelagh
AU - Elyas, Basil
AU - Lilley, Margaret
AU - Bamforth, Steven
AU - McDermid, Heather E.
N1 - Funding Information:
We thank John Armour for providing control MAPH probes and invaluable advice. We also thank John Gaspar, for performing the microsatellite analysis of patient 4; Catherine Kashork (Baylor College of Medicine, Houston, TX), for performing the FISH analysis of patient 4; Lucy Osborne, for helpful discussions; and Jack Scott, for help with the figures. H.E.M. was supported by a grant from the Canadian Institutes of Health Research (MOP11639). This work was also supported by the March of Dimes (1-FY00-768 [to B.E.M.]) and the National Institutes of Health (1 P01 HD39420-01 [to B.E.M. and L.G.S.] and 5 P01 HD34980-05 [to B.E.M.]). This study was approved by the Health Research Ethics Board of the University of Alberta Health Sciences Faculties.
PY - 2005/5
Y1 - 2005/5
N2 - 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.
AB - 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.
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U2 - 10.1086/429841
DO - 10.1086/429841
M3 - Article
C2 - 15800846
AN - SCOPUS:20244383760
SN - 0002-9297
VL - 76
SP - 865
EP - 876
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -