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Introduction: Congenital heart disease (CHD) is the most common type of congenital defect reported to be one of the leading causes of mortality in the first year of life. Microdeletion and microduplication syndromes (MMS) are associated with cardiac malformations. Understanding which genetic factors are involved in these conditions directly impacts treatment decisions. We aimed to identify the occurrence of genetic alterations and their association with MMS in CHD pediatric patients evaluated in a reference service of Southern Brazil. Methods: Participants were recruited during 2010 in the intensive care unit of a pediatric hospital. MMs and regions of chromosome 22 were screened by SALSA MLPA Probemix P245 Microdeletion Syndromes-1A kit for detection of copy number variations (CNVs). Results: MMS were detected in 11 from 207 patients (5.3%). Heterozygous deletion in the 22q11.2 chromosome region was the most prevalent CNV (5 from 11 patients). Also, atypical RTDR1 deletion and 22q11.2 duplication were detected. MLPA was able to reveal microdeletions in SNRPN and NF1 genes in patients with a normal karyotype and FISH. Conclusion: Our study reports the prevalence and variability of genomic alterations associated with MMS in CHD pediatric patients. The results by MLPA are of great help in planning and specialized care.

Wnt/β-catenin has been described as crucial for dorsal-ventral and antero-posterior patterning, playing multiple roles at different stages of development. Cholesterol-rich membrane microdomains (CRMMs), cholesterol- and sphingolipid-enriched domains of the plasma membrane, are known as platforms for signaling pathways. Although we have demonstrated the importance of the CRMMs for head development, how they participate in prechordal plate formation and embryo axis patterning remains an open question. Moreover, the participation of the CRMMs in the Wnt/β-catenin signaling pathway activity in vivo is unclear, particularly during embryonic development. In this study, we demonstrated that CRMMs disruption by methyl-beta-cyclodextrin (MβCD) potentiates the activation of the Wnt/β-catenin signaling pathway in vitro and in vivo during embryonic development, causing head defects by expanding the Wnt expression domain. Furthermore, we also found that the action of CRMMs depends on the microenvironmental context because it also works in conjunction with dkk1, when dkk1 is overexpressed. Thus, we propose CRMMs as a further mechanism of prechordal plate protection against the Wnt signals secreted by posterolateral cells, complementing the action of secreted antagonists.