Luiza Emy Dorfman1, Júlio César L Leite2, Roberto Giugliani3, Mariluce Riegel4. 1. Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. 2. Serviço de Genética Médica, Hospital de Clínicas, Porto Alegre, RS, Brazil. 3. 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. 4. 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.
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.
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: Hugo Hernán Abarca Barriga; Felix Chavesta Velásquez; Claudia Barletta Carrillo; Abel Paucarmayta Tacuri; Margaret Bazán Hurtado; Tania Vásquez Loarte; Luis Ordoñez Rondón; Marco Ordoñez Linares; Evelina Andrea Rondón Abuhadba Journal: Rev Fac Cien Med Univ Nac Cordoba Date: 2022-06-06
Authors: Roberto Giugliani; Filippo P Vairo; Mariluce Riegel; Carolina F M de Souza; Ida V D Schwartz; Sérgio D J Pena Journal: Orphanet J Rare Dis Date: 2016-06-10 Impact factor: 4.123
Authors: Elaine Lustosa-Mendes; Ana P Dos Santos; Társis P Vieira; Erlane M Ribeiro; Adriana A Rezende; Agnes C Fett-Conte; Denise P Cavalcanti; Têmis M Félix; Isabella L Monlleó; Vera Lúcia Gil-da-Silva-Lopes Journal: J Pediatr (Rio J) Date: 2020-07-21 Impact factor: 2.990