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Is HSPG2 a modifier gene for Marfan syndrome?
European Journal of Human Genetics ( IF 3.7 ) Pub Date : 2020-06-08 , DOI: 10.1038/s41431-020-0666-0
Isabela Gerdes Gyuricza 1 , Rodrigo Barbosa de Souza 1 , Luis Ernesto Farinha-Arcieri 1 , Gustavo Ribeiro Fernandes 1 , Lygia Veiga Pereira 1
Affiliation  

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.



中文翻译:


HSPG2 是马凡综合征的修饰基因吗?



马凡综合征 (MFS) 是一种由FBN1基因变异引起的结缔组织疾病。然而,其他基因影响该疾病的表现,其特征是即使在家庭内部也具有很高的临床变异性。我们在 MFS 的 mgΔ loxPneo小鼠模型中绘制了心血管和骨骼表现的修饰基因座以及人类基因组中的合成基因座。证实了我们的发现,这些基因座之一也被确定为 MFS 患者的修饰基因座。在这里,我们研究了位于该区域的HSPG2基因,作为 MFS 的候选修饰基因。我们展示了非等基因 mgΔ loxPneo小鼠脊柱和主动脉中Fbn1Hspg2表达之间的相关性。此外,我们发现,具有严重表型的小鼠的Hspg2表达量低于轻度受影响的小鼠。因此,我们建议HSPG2是 MFS 的一个强有力的候选修饰基因,并且应该在患者中研究其在调节疾病严重程度中的作用。

更新日期:2020-06-08
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