title: Microarray-based comparative genomic hybridization analysis in neonates with congenital anomalies: detection of chromosomal imbalances.
abstract: OBJECTIVE
  To identify chromosomal imbalances by whole-genome microarray-based comparative genomic hybridization (array-CGH) in DNA samples of neonates with congenital anomalies of unknown cause from a birth defects monitoring program at a public maternity hospital.
  
  
  METHODS
  A blind genomic analysis was performed retrospectively in 35 stored DNA samples of neonates born between July of 2011 and December of 2012. All potential DNA copy number variations detected (CNVs) were matched with those reported in public genomic databases, and their clinical significance was evaluated.
  
  
  RESULTS
  Out of a total of 35 samples tested, 13 genomic imbalances were detected in 12/35 cases (34.3%). In 4/35 cases (11.4%), chromosomal imbalances could be defined as pathogenic; in 5/35 (14.3%) cases, DNA CNVs of uncertain clinical significance were identified; and in 4/35 cases (11.4%), normal variants were detected. Among the four cases with results considered causally related to the clinical findings, two of the four (50%) showed causative alterations already associated with well-defined microdeletion syndromes. In two of the four samples (50%), the chromosomal imbalances found, although predicted as pathogenic, had not been previously associated with recognized clinical entities.
  
  
  CONCLUSIONS
  Array-CGH analysis allowed for a higher rate of detection of chromosomal anomalies, and this determination is especially valuable in neonates with congenital anomalies of unknown etiology, or in cases in which karyotype results cannot be obtained. Moreover, although the interpretation of the results must be refined, this method is a robust and precise tool that can be used in the first-line investigation of congenital anomalies, and should be considered for prospective/retrospective analyses of DNA samples by birth defect monitoring programs.
authors.affiliation: Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Luiza
authors.initials: L
authors.lastname: Emy Dorfman
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas, Porto Alegre, RS, Brazil.
authors.forename: Júlio César L
authors.initials: JC
authors.lastname: Leite
authors.affiliation: Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas, Porto Alegre, RS, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas, Porto Alegre, RS, Brazil. Electronic address: mriegel@hcpa.ufrgs.br.
authors.forename: Mariluce
authors.initials: M
authors.lastname: Riegel
mesh_terms: D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods*; D000013:Congenital Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012189:Retrospective Studies
keywords: Anomalias congênitas; Anomalias cromossômicas; Array-CGH; Birth defects; CGH-array; Chromosomal abnormalities; Citogenética molecular; Congenital anomalies; Defeitos congênitos; Molecular cytogenetics; Newborn selective screening; Triagem seletiva de recém-nascidos