title: Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region.
abstract: Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21-q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations.
authors.affiliation: Signature Genomic Laboratories, LLC, Spokane, WA 99207, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Coppinger
authors.forename: Donna
authors.initials: D
authors.lastname: McDonald-McGinn
authors.forename: Elaine
authors.initials: E
authors.lastname: Zackai
authors.forename: Kate
authors.initials: K
authors.lastname: Shane
authors.forename: Joan F
authors.initials: JF
authors.lastname: Atkin
authors.forename: Alexander
authors.initials: A
authors.lastname: Asamoah
authors.forename: Robert
authors.initials: R
authors.lastname: Leland
authors.forename: David D
authors.initials: DD
authors.lastname: Weaver
authors.forename: Susan
authors.initials: S
authors.lastname: Lansky-Shafer
authors.forename: Karen
authors.initials: K
authors.lastname: Schmidt
authors.forename: Heidi
authors.initials: H
authors.lastname: Feldman
authors.forename: William
authors.initials: W
authors.lastname: Cohen
authors.forename: Judy
authors.initials: J
authors.lastname: Phalin
authors.forename: Berkley
authors.initials: B
authors.lastname: Powell
authors.forename: Blake C
authors.initials: BC
authors.lastname: Ballif
authors.forename: Aaron
authors.initials: A
authors.lastname: Theisen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Geiger
authors.forename: Chad
authors.initials: C
authors.lastname: Haldeman-Englert
authors.forename: Tamim H
authors.initials: TH
authors.lastname: Shaikh
authors.forename: Sulagna
authors.initials: S
authors.lastname: Saitta
authors.forename: Bassem A
authors.initials: BA
authors.lastname: Bejjani
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D004062:DiGeorge Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis