Is HSPG2 a modifier gene for Marfan syndrome?

Isabela Gerdes Gyuricza, Rodrigo Barbosa de Souza, Luis Ernesto Farinha-Arcieri, Gustavo Ribeiro Fernandes, Lygia Veiga Pereira

European journal of human genetics : EJHG 2020 Sep

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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.

Citation

Isabela Gerdes Gyuricza, Rodrigo Barbosa de Souza, Luis Ernesto Farinha-Arcieri, Gustavo Ribeiro Fernandes, Lygia Veiga Pereira. Is HSPG2 a modifier gene for Marfan syndrome? European journal of human genetics : EJHG. 2020 Sep;28(9):1292-1296