{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:13:01Z","timestamp":1789665181558,"version":"4.0.1"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T00:00:00Z","timestamp":1591574400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T00:00:00Z","timestamp":1591574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/18255-3"],"award-info":[{"award-number":["2016\/18255-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Marfan syndrome (MFS) is a connective tissue disease caused by variants in the\n                    <jats:italic>FBN1<\/jats:italic>\n                    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\u2206\n                    <jats:sup>loxPneo<\/jats:sup>\n                    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\n                    <jats:italic>HSPG2<\/jats:italic>\n                    gene, located in this region, as a candidate modifier gene for MFS. We show a correlation between\n                    <jats:italic>Fbn1<\/jats:italic>\n                    and\n                    <jats:italic>Hspg2<\/jats:italic>\n                    expression in spinal column and aorta in non-isogenic mg\u2206\n                    <jats:sup>loxPneo<\/jats:sup>\n                    mice. Moreover, we show that mice with severe phenotypes present lower expression of\n                    <jats:italic>Hspg2<\/jats:italic>\n                    than those mildly affected. Thus, we propose that\n                    <jats:italic>HSPG2<\/jats:italic>\n                    is a strong candidate modifier gene for MFS and its role in modulating disease severity should be investigated in patients.\n                  <\/jats:p>","DOI":"10.1038\/s41431-020-0666-0","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T06:05:56Z","timestamp":1591596356000},"page":"1292-1296","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Is HSPG2 a modifier gene for Marfan syndrome?"],"prefix":"10.1038","volume":"28","author":[{"given":"Isabela","family":"Gerdes Gyuricza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Barbosa de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Ernesto","family":"Farinha-Arcieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Ribeiro Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0002-725X","authenticated-orcid":false,"given":"Lygia","family":"Veiga Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,8]]},"reference":[{"key":"666_CR1","doi-asserted-by":"crossref","unstructured":"Ramirez F, Dietz HC. 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