title: Atypical copy number abnormalities in 22q11.2 region: report of three cases.
abstract: The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, with a highly variable phenotype. This chromosomal region contains low copy repeat (LCR) sequences that mediate non-allelic homologous recombination which predispose to copy number abnormalities at this locus. This article describes three patients investigated for suspicion of 22q11.2DS presenting atypical copy number abnormalities overlapping or not with the common ∼3 Mb deletion. They were investigated by G-banding karyotype, Multiplex-ligation dependent probe amplification (MLPA) and array Genomic Hibridization (aGH). Clinical and molecular data were compared with literature, in order to contribute to genotype-phenotype correlation. Atypical chromosomal abnormalities were detected: 3.6 Mb deletion at 22q11.21-q11.23 between LCRs B-F in patient 1 and approximately 1.5 Mb deletion at 22q11.21-q11.22 between LCRs D-E in patients 2 and 3. The breakpoints detected in patient 1 have not been previously described. These findings exemplify the complexity and genetic heterogeneity observed in 22q11.2 region and corroborates the idea that genetic modifiers contribute to the phenotypic variability observed in proximal and distal 22q11.2 deletion syndromes.
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas (UNICAMP), Brazil.
authors.forename: Miriam Coelho
authors.initials: MC
authors.lastname: Molck
authors.forename: Társis Paiva
authors.initials: TP
authors.lastname: Vieira
authors.forename: Ilária Cristina
authors.initials: IC
authors.lastname: Sgardioli
authors.forename: Milena
authors.initials: M
authors.lastname: Simioni
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Dos Santos
authors.forename: Josiane
authors.initials: J
authors.lastname: Souza
authors.forename: Fabíola Paoli
authors.initials: FP
authors.lastname: Monteiro
authors.forename: Vera Lúcia
authors.initials: VL
authors.lastname: Gil-da-Silva-Lopes
mesh_terms: D058165:22q11 Deletion Syndrome / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D010641:Phenotype; D056916:Segmental Duplications, Genomic
keywords: 22q11.2 deletion; Array genomic Hybridization; Atypical copy number abnormalities; Distal 22q11.2 deletion; Genotype–phenotype correlation; Multiplex-ligation dependent probe amplification