Genomic imbalances in syndromic congenital heart disease.
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.


CONCLUSIONS
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.
Universidade Estadual de Campinas (UNICAMP), Departamento de Genética Médica, Campinas, SP, Brazil.
Miriam Coelho
MC
Molck
Universidade Estadual de Campinas (UNICAMP), Departamento de Genética Médica, Campinas, SP, Brazil.
Milena
M
Simioni
Universidade Estadual de Campinas (UNICAMP), Departamento de Genética Médica, Campinas, SP, Brazil.
Társis
T
Paiva Vieira
Universidade Estadual de Campinas (UNICAMP), Departamento de Genética Médica, Campinas, SP, Brazil.
Ilária Cristina
IC
Sgardioli
Universidade Estadual de Campinas (UNICAMP), Departamento de Genética Médica, Campinas, SP, Brazil.
Fabíola
F
Paoli Monteiro
Centro de Atendimento Integral ao Fissurado Lábio Palatal (CAIF), Curitiba, PR, Brazil.
Josiane
J
Souza
Faculdade de Medicina de São José do Rio Preto, Departamento de Biologia Molecular, São José do Rio Preto, SP, Brazil.
Agnes Cristina
AC
Fett-Conte
Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre, RS, Brazil.
Têmis Maria
TM
Félix
Universidade Federal de Alagoas (UFAL), Hospital Universitário, Faculdade de Medicina, Serviço de Genética Clínica, Maceió, AL, Brazil.
Isabella
I
Lopes Monlléo
Universidade Estadual de Campinas (UNICAMP), Departamento de Genética Médica, Campinas, SP, Brazil. Electronic address: vlopes@fcm.unicamp.br.
Vera Lúcia
VL
Gil-da-Silva-Lopes
D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D023281:Genomics; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis
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