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MFS is caused by dominant negative (DN) and haploinsufficient (HI) mutations of the<jats:italic>FBN1<\/jats:italic>gene. Our aim was to identify mutations of MFS patients with high detection rate and to investigate the use of a gene panel for patients with Marfanoid habitus. We also aimed to examine correlations between genotype and cardiovascular manifestations to predict \u201cmalignant\u201d mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>136 individuals were enrolled. In the first phase, next-generation sequencing (NGS) and Sanger sequencing were performed for 57 patients to screen the<jats:italic>FBN1<\/jats:italic>gene, followed by multiplex ligation-dependent probe amplification (MLPA) in negative cases. For repeated negative results, NGS gene panel involving 9 genes was used. In the second phase, 79 patients were tested primarily with the same gene panel, negative samples were tested by MLPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>84 pathogenic mutations were detected, out of which 78 affected<jats:italic>FBN1<\/jats:italic>, 6 non-<jats:italic>FBN1<\/jats:italic>mutations (2<jats:italic>TGFB2<\/jats:italic>, 1<jats:italic>TGFBR2<\/jats:italic>, 2<jats:italic>TGFBR1<\/jats:italic>, 1<jats:italic>SMAD3<\/jats:italic>) are associated with Loeys-Dietz syndrome (LDS). LDS patients had lower systemic score and they were younger, but their aortic involvement did not differ. MLPA detected 4 multi-exon deletions of<jats:italic>FBN1<\/jats:italic>gene, which could not be identified by our first-step screening method. Aortic involvement (aortic dissection and\/or dilation) did not differ significantly among HI and DN mutations (<jats:italic>p<\/jats:italic>\u2009=\u20090.061). Combined group of HI and DN mutations eliminating a disulphide-bonding cysteine (DN Cys) had significantly higher aortic involvement rate than DN mutations not eliminating a disulphide-bonding cysteine (DN non-Cys) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Patients with DN Cys required significantly more aortic surgeries than HI and DN non-Cys mutations (<jats:italic>p<\/jats:italic>\u2009=\u20090.042 and<jats:italic>p<\/jats:italic>\u2009=\u20090.015, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Due to the relevant number of mutations affecting genes other than<jats:italic>FBN1<\/jats:italic>, preferred approach for testing individuals with Marfanoid habitus is using a gene panel rather than single-gene analysis, followed by MLPA for negative samples. DN Cys and HI mutations should be considered as risk factors for aortic involvement. Genetic testing for patients with Marfanoid features and a systemic score under 7 is recommended, as LDS patients may have lower scores, but they may have severe cardiovascular manifestations.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13023-020-01569-4","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T09:02:47Z","timestamp":1602752567000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Optimising the mutation screening strategy in Marfan syndrome and identifying genotypes with more severe aortic involvement"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6695-9877","authenticated-orcid":false,"given":"Roland","family":"Stengl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"Bors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6492-0426","authenticated-orcid":false,"given":"Bence","family":"\u00c1gg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"P\u00f3los","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Matyas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ria Judit","family":"Moln\u00e1r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint","family":"Fekete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f3ra","family":"Csab\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajnalka","family":"Andrikovics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9la","family":"Merkely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Radovits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Szabolcs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e1lm\u00e1n","family":"Benke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"issue":"9501","key":"1569_CR1","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1016\/S0140-6736(05)67789-6","volume":"366","author":"DP Judge","year":"2005","unstructured":"Judge DP, Dietz HC. 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