Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome

Chantal Sellier, Vicki J. Hwang, Ravi Dandekar, Blythe Durbin-Johnson, Nicolas Charlet-Berguerand, Bradley Ander, Frank R Sharp, Kathleen Angkustsiri, Tony J Simon, Flora Tassone

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Deletion of the 1.5-3 Mb region of chromosome 22 at locus 11.2 gives rise to the chromosome 22q11.2 deletion syndrome (22q11DS), also known as DiGeorge and Velocardiofacial Syndromes. It is the most common micro-deletion disorder in humans and one of the most common multiple malformation syndromes. The syndrome is characterized by a broad phenotype, whose characterization has expanded considerably within the last decade and includes many associated findings such as craniofacial anomalies (40%), conotruncal defects of the heart (CHD; 70-80%), hypocalcemia (20-60%), and a range of neurocognitive anomalies with high risk of schizophrenia, all with a broad phenotypic variability. These phenotypic features are believed to be the result of a change in the copy number or dosage of the genes located in the deleted region. Despite this relatively clear genetic etiology, very little is known about which genes modulate phenotypic variations in humans or if they are due to combinatorial effects of reduced dosage of multiple genes acting in concert. Here, we report on decreased expression levels of genes within the deletion region of chromosome 22, including DGCR8, in peripheral leukocytes derived from individuals with 22q11DS compared to healthy controls. Furthermore, we found dysregulated miRNA expression in individuals with 22q11DS, including miR-150, miR-194 and miR-185. We postulate this to be related to DGCR8 haploinsufficiency as DGCR8 regulates miRNA biogenesis. Importantly we demonstrate that the level of some miRNAs correlates with brain measures, CHD and thyroid abnormalities, suggesting that the dysregulated miRNAs may contribute to these phenotypes and/or represent relevant blood biomarkers of the disease in individuals with 22q11DS.

Original languageEnglish (US)
Article numbere103884
JournalPLoS One
Volume9
Issue number8
DOIs
StatePublished - Aug 1 2014

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DiGeorge Syndrome
MicroRNAs
microRNA
Chromosomes
Genes
chromosomes
phenotype
chromosome elimination
gene dosage
Chromosomes, Human, Pair 22
hypocalcemia
Gene Dosage
genes
dosage
phenotypic variation
etiology
leukocytes
biomarkers
Biomarkers
heart

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. / Sellier, Chantal; Hwang, Vicki J.; Dandekar, Ravi; Durbin-Johnson, Blythe; Charlet-Berguerand, Nicolas; Ander, Bradley; Sharp, Frank R; Angkustsiri, Kathleen; Simon, Tony J; Tassone, Flora.

In: PLoS One, Vol. 9, No. 8, e103884, 01.08.2014.

Research output: Contribution to journalArticle

Sellier C, Hwang VJ, Dandekar R, Durbin-Johnson B, Charlet-Berguerand N, Ander B et al. Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. PLoS One. 2014 Aug 1;9(8). e103884. https://doi.org/10.1371/journal.pone.0103884
Sellier, Chantal ; Hwang, Vicki J. ; Dandekar, Ravi ; Durbin-Johnson, Blythe ; Charlet-Berguerand, Nicolas ; Ander, Bradley ; Sharp, Frank R ; Angkustsiri, Kathleen ; Simon, Tony J ; Tassone, Flora. / Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. In: PLoS One. 2014 ; Vol. 9, No. 8.
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