title: Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil.
abstract: In several patients, intellectual disability and/or congenital malformation may be attributed to chromosomal changes. In this study, we conducted an array-CGH test of 200 patients from the Northeast of Brazil with intellectual disability and/or congenital malformation. Blood samples were collected from the proband and from their parents when possible. DNA was extracted and investigated using the array-CGH test. Findings were evaluated for the pathogenicity in databases of benign and pathogenic changes (ISCA, UCSC, DGV, and DECIPHER). Forty-seven copy number variations (CNVs) were identified in 43/200 (21.5%) patients, including 25/98 (25.5%) in males and 22/102 (21.57%) in females. We considered 33 of these to be clinically significant, reaching a diagnosis rate of 16.5%. The sizes of the CNVs varied from 102 kb to 24 Mb in deletions and from 115 kb to 140 Mb in duplications. In 10/47 (21.3%) patients, the rearrangement involved a sex chromosome. Thirty-nine patients had one chromosomal aberration, while 2 concomitant abnormalities were detected in 4 patients. Ten of 47 CNVs (21.3%) were > 5Mb in size. Fifteen patients had CNVs related to known syndromes. This research highlights the contribution of submicroscopic chromosomal changes to the etiology of intellectual disability and/or congenital malformation, particularly the implication of chromosomal abnormalities detected using an array-CGH test, with a high rate of 16.5%. Thus, our results support the use of array-CGH replacing standard karyotype as the first-tier cytogenetic diagnostic test for patients with multiple congenital anomalies and/or intellectual disability.
authors.affiliation: Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brasil.
authors.forename: G S
authors.initials: GS
authors.lastname: Vianna
authors.affiliation: Universidade Federal de Campina Grande, Campina Grande, PB, Brasil.
authors.forename: P F V
authors.initials: PF
authors.lastname: Medeiros
authors.affiliation: Universidade Federal de Campina Grande, Campina Grande, PB, Brasil.
authors.forename: A F
authors.initials: AF
authors.lastname: Alves
authors.affiliation: Universidade Federal de Campina Grande, Campina Grande, PB, Brasil.
authors.forename: T O
authors.initials: TO
authors.lastname: Silva
authors.affiliation: Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brasil.
authors.forename: F S
authors.initials: FS
authors.lastname: Jehee
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D001938:Brazil; D002648:Child; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D004247:DNA / Q000235:genetics*; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D007621:Karyotyping; D008297:Male
chemical_list: D004247:DNA