Miriam Coelho Molck1, Milena Simioni1, Társis Paiva Vieira1, Ilária Cristina Sgardioli1, Fabíola Paoli Monteiro1, Josiane Souza2, Agnes Cristina Fett-Conte3, Têmis Maria Félix4, Isabella Lopes Monlléo5, Vera Lúcia Gil-da-Silva-Lopes6. 1. Universidade Estadual de Campinas (UNICAMP), Departamento de Genética Médica, Campinas, SP, Brazil. 2. Centro de Atendimento Integral ao Fissurado Lábio Palatal (CAIF), Curitiba, PR, Brazil. 3. Faculdade de Medicina de São José do Rio Preto, Departamento de Biologia Molecular, São José do Rio Preto, SP, Brazil. 4. Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre, RS, Brazil. 5. Universidade Federal de Alagoas (UFAL), Hospital Universitário, Faculdade de Medicina, Serviço de Genética Clínica, Maceió, AL, Brazil. 6. Universidade Estadual de Campinas (UNICAMP), Departamento de Genética Médica, Campinas, SP, Brazil. Electronic address: vlopes@fcm.unicamp.br.
Abstract
OBJECTIVE: To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). METHODS: 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA). RESULTS: Clinically significant copy number variations (CNVs ≥300kb) were identified in 10% (8/78) of cases. In addition, potentially relevant CNVs were detected in two cases (993kb duplication in 15q21.1 and 706kb duplication in 2p22.3). Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD. CONCLUSION: These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD.
OBJECTIVE: To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). METHODS: 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA). RESULTS: Clinically significant copy number variations (CNVs ≥300kb) were identified in 10% (8/78) of cases. In addition, potentially relevant CNVs were detected in two cases (993kb duplication in 15q21.1 and 706kb duplication in 2p22.3). Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD. CONCLUSION: These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD.
Keywords:
22q11 deletion syndrome; Aberrações cromossômicas; Cardiopatias congênitas; Chromosome aberrations; Comparative genomic hybridization; Congenital heart defects; DNA copy number variations; Hibridização genômica comparativa; Síndrome de deleção 22q11; Variações do número de cópias de DNA
Authors: Jared M McLendon; Xiaoming Zhang; Daniel S Matasic; Mohit Kumar; Olha M Koval; Isabella M Grumbach; Sakthivel Sadayappan; Barry London; Ryan L Boudreau Journal: J Am Heart Assoc Date: 2022-06-22 Impact factor: 6.106