Partial microduplication in the histone acetyltransferase complex member KANSL1 is associated with congenital heart defects in 22q11.2 microdeletion syndrome patients
Author
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León, Luis
Author
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Benavides, Felipe
Author
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Espinoza, Karena
Author
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Vial, Cecilia
Author
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Alvarez Zenteno, Patricia
Author
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Lay Son, Guillermo
Author
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Miranda, Macarena
Author
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Repetto, Gabriela
Admission date
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2019-06-12T20:38:46Z
Available date
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2019-06-12T20:38:46Z
Publication date
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2017
Cita de ítem
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Scientific Reports 7: 1795
es_ES
Identifier
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20452322
Identifier
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10.1038/s41598-017-01896-w
Identifier
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https://repositorio.uchile.cl/handle/2250/169900
Abstract
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22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion disorder in humans, with an incidence of 1/4000 live births. It is caused by a heterozygous deletion of 1.5-3 Mb on chromosome region 22q11.2. Patients with the deletion present features that include neuropsychiatric problems, craniofacial abnormalities and cardiovascular malformations. However, the phenotype is highly variable and the factors related to the clinical heterogeneity are not fully understood. About 65% of patients with 22q11.2DS have congenital heart defects (CHD). The main goal of this study was to identify common CNVs in 22q11.2DS patients that could be associated with the incomplete penetrance of CHD. Analysis of genomic DNA from 253 patients with 22q11.2DS using array technology showed an association between a microduplication located in region 17q21.31 and CHD (p-value = 0.023, OR = 2.75, 95% CI = 1.17-7.03). This region includes the first three exons of KANSL1 gene. Bioinformatic analysis showed that KANSL1 and CRKL, a gene in the commonly deleted region of 22q11.2DS, are part of the same regulatory module in a miRNA-mRNA network. These results show that a KANSL1 microduplication, in combination with the 22q11.2 deletion, is associated with increased risk of CHD in these patients, suggesting that KANSL1 plays a role as a modifier gene in 22q11.2DS patients
Partial microduplication in the histone acetyltransferase complex member KANSL1 is associated with congenital heart defects in 22q11.2 microdeletion syndrome patients