Abstract
Pallister-Killian syndrome is a multisystem sporadic genetic diagnosis characterized by facial dysmorphia, variable developmental delay and intellectual impairment, hypotonia, seizures, diaphragmatic hernia, and other systemic abnormalities. Pallister-Killian syndrome is typically caused by the presence of a supernumerary isochromosome that is always present in a tissue limited mosaic pattern, resulting in tetrasomy 12p due to the two extra copies of 12p. We evaluated the potential contribution of microRNAs located on 12p to the pathogenesis of Pallister-Killian syndrome phenotype. Using skin fibroblast cell lines from 13 probands with Pallister-Killian syndrome and 5 normal matched controls, the expression level of 5 microRNAs located on 12p and their target gene mRNA levels were measured. All measured micro RNAs located on 12p were overexpressed in Pallister-Killian syndrome fibroblasts, although the fold difference of the expression level was lower than copy number differences. Among the five microRNAs, miR-1244 had the highest fold difference. Many of computer-predicted target genes of miR-1244 were downregulated in Pallister-Killian syndrome skin fibroblasts. In particular, expression levels of MEIS2 and UQCRB were significantly decreased in Pallister-Killian syndrome samples, and an inverse linear correlation was seen between the level of miR-1244 and MEIS2 and UQCRB expression levels. Since many of computer-predicted miR-1244 target genes play roles in transcriptional regulation, overexpression of miR-1244 due to tetrasomy 12p may contribute to the pleiotropic phenotype of Pallister-Killian syndrome by modulating its downstream target genes including MEIS2 and UQCRB.
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Abbreviations
- Pallister-Killian Syndrome:
-
PKS
- MicroRNAs:
-
miRNAs
- Untranslated region:
-
UTR
- Droplet digital PCR:
-
DDPCR
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Acknowledgments
We are deeply indebted to the PKS families who participated in this study as well as support from the PKS Kids family support group, and The Children’s Hospital of Philadelphia institutional development funds (IDK). We also thank Drs. Adam Zahm, Nicholas Hand, Joshua Friedman, and Matthew Deardorff for their helpful suggestions on experimental design and interpretation of the data.
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Responsible Editor: Matthew Breen.
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Online resource 1
microRNAs and genes whose transcript levels were measured in this study (DOC 63 kb)
Online resource 2
Expression profile of miR-141 and miR-200c. Number represents the total number of sequenced miRNAs. (DOC 218 kb)
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Izumi, K., Zhang, Z., Kaur, M. et al. 12p microRNA expression in fibroblast cell lines from probands with Pallister-Killian syndrome. Chromosome Res 22, 453–461 (2014). https://doi.org/10.1007/s10577-014-9431-y
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DOI: https://doi.org/10.1007/s10577-014-9431-y