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Published on: July 14, 2016
Is HSPG2 a modifier gene for Marfan syndrome?
Isabela Gerdes Gyuricza1, Rodrigo Barbosa de Souza1, Luis Ernesto Farinha-Arcieri1
1National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, SP, 05508-900, Brazil.
Abstract:
Marfan syndrome (MFS) is a connective tissue disease caused by variants in the FBN1 gene. Nevertheless, other genes influence the manifestations of the disease, characterized by high clinical variability even within families. We mapped modifier loci for cardiovascular and skeletal manifestations in the mg∆loxPneo mouse model for MFS and the synthenic loci in the human genome. Corroborating our findings, one of those loci was identified also as a modifier locus in MFS patients. Here, we investigate the HSPG2 gene, located in this region, as a candidate modifier gene for MFS. We show a correlation between Fbn1 and Hspg2 expression in spinal column and aorta in non-isogenic mg∆loxPneo mice. Moreover, we show that mice with severe phenotypes present lower expression of Hspg2 than those mildly affected. Thus, we propose that HSPG2 is a strong candidate modifier gene for MFS and its role in modulating disease severity should be investigated in patients.
Insights
Marfan syndrome (MFS) severity is influenced by other genes. Researchers identified the HSPG2 gene as a potential modifier, showing its expression correlates with disease severity in mouse models.
Area of Science:
- Genetics
- Molecular Biology
- Medical Research
Background:
- Marfan syndrome (MFS) is a genetic connective tissue disorder caused by FBN1 gene variants.
- MFS exhibits significant clinical variability, suggesting the influence of modifier genes.
- Previous studies identified modifier loci for MFS manifestations in mouse models and humans.
Purpose of the Study:
- To investigate the HSPG2 gene as a candidate modifier for Marfan syndrome.
- To explore the relationship between FBN1 and HSPG2 gene expression in MFS.
- To assess the correlation between HSPG2 expression levels and MFS disease severity.
Main Methods:
- Mapping modifier loci in the mgΔloxPneo mouse model and synthenic human loci.
- Analyzing Fbn1 and Hspg2 gene expression in the spinal column and aorta of mice.
- Comparing Hspg2 expression in mice with severe versus mild MFS phenotypes.
Main Results:
- A modifier locus was identified in both MFS mouse models and human patients.
- A correlation was observed between Fbn1 and Hspg2 expression in mouse tissues.
- Mice with more severe MFS phenotypes showed lower Hspg2 expression.
Conclusions:
- HSPG2 is proposed as a strong candidate modifier gene for Marfan syndrome.
- The study suggests HSPG2 plays a role in modulating MFS disease severity.
- Further investigation of HSPG2 in MFS patients is warranted.
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