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Congenital contractural arachnodactyly syndrome (CCA) is an autosomal dominant hereditary disease of connective tissue. To date, the <jats:italic>FBN2<\/jats:italic> gene is the only gene reported to cause CCA. Researchers found that <jats:italic>COL1A2<\/jats:italic> and <jats:italic>FBN2<\/jats:italic> are both involved in the extracellular matrix organization pathway. These findings suggest that these two genes play an important role in a similar mechanism and may trigger a synergistic effect.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Trio-whole-exome sequencing (Trio-WES) was performed to analyse the underlying genetic cause of a proband with OI in a Chinese family. Sanger sequencing was used to validate the mutations in 3 members of the family with OI with varying degrees of severity of skeletal abnormalities and the members with no clinical signs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Result<\/jats:title>\n                <jats:p>A c.3304G\u2009&gt;\u2009C mutation in the <jats:italic>COL1A2<\/jats:italic> gene (p.Gly1102Arg) and a novel c.4108G\u2009&gt;\u2009T mutation in the <jats:italic>FBN2<\/jats:italic> gene (p.Glu1370*) were detected in the proband, an affected member of the family. The affected individuals with both mutations present a more severe phenotype, while affected individuals present a milder phenotype if only the mutation in <jats:italic>COL1A2<\/jats:italic> is detected (c.3304G\u2009&gt;\u2009C). The unaffected individual in this family did not have any mutations in the <jats:italic>COL1A2<\/jats:italic> gene or <jats:italic>FBN2<\/jats:italic> gene.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our study is the first clinical report to indicate that patients carrying concomitant mutations in both the <jats:italic>COL1A2<\/jats:italic> and <jats:italic>FBN2<\/jats:italic> genes may present with more severe skeletal abnormalities. Furthermore, our study suggests the possibility of synergistic effects between the <jats:italic>COL1A2<\/jats:italic> and <jats:italic>FBN2<\/jats:italic> genes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-022-01296-8","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T13:05:05Z","timestamp":1657285505000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Carrying both COL1A2 and FBN2 gene heterozygous mutations results in a severe skeletal clinical phenotype: an affected family"],"prefix":"10.1186","volume":"15","author":[{"given":"Jing","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinqin","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bocheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanbing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"1296_CR1","first-page":"540178","volume":"2011","author":"IB Amor","year":"2011","unstructured":"Amor IB, Glorieux FH, Rauch F. 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Written informed consent was obtained from the patients and their parents, who agreed to join this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All patients and their parents signed the informed consent during the counseling sessions and agreed to share their variant data in a reputable scientific journal. The patient\u2019s parents provided the written consent for the manuscript to be published. Informed consent from parents regarding data and clinical details for publication has been obtained.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"154"}}