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The majority of affected individuals have aortopathies associated with early mortality and morbidity. Implementation of targeted gene panel next-generation sequencing in these individuals is a powerful tool to obtain a genetic diagnosis. Here, we report on clinical and genetic spectrum of 53 families from India with a total of 83 patients who had a clinical diagnosis suggestive of Marfan syndrome or related disorders. We obtained a molecular diagnosis in 45\/53 (85%) index patients, in which 36\/53 (68%) had rare variants in <jats:italic>FBN1<\/jats:italic> (Marfan syndrome; 63 patients in total), seven (13.3%) in <jats:italic>TGFBR1<\/jats:italic>\/<jats:italic>TGFBR2<\/jats:italic> (Loeys\u2013Dietz syndrome; nine patients in total) and two patients (3.7%) in <jats:italic>SKI<\/jats:italic> (Shprintzen\u2013Goldberg syndrome). 21 of 41 rare variants (51.2%) were novel. We did not detect a disease-associated variant in 8 (15%) index patients, and none of them met the Ghent Marfan diagnostic criteria. We found the homozygous <jats:italic>FBN1<\/jats:italic> variant p.(Arg954His) in a boy with typical features of Marfan syndrome. Our study is the first reporting on the spectrum of variants in <jats:italic>FBN1, TGFBR1, TGFBR2<\/jats:italic>, and <jats:italic>SKI<\/jats:italic> in Indian individuals.<\/jats:p>","DOI":"10.1038\/s41598-020-80755-7","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T19:24:12Z","timestamp":1610479452000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinically relevant variants in a large cohort of Indian patients with Marfan syndrome and related disorders identified by next-generation sequencing"],"prefix":"10.1038","volume":"11","author":[{"given":"Shalini S.","family":"Nayak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline E.","family":"Schneeberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siddaramappa J.","family":"Patil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karegowda M.","family":"Arun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pujar V.","family":"Suresh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viralam S.","family":"Kiran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sateesh","family":"Siddaiah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shreesha","family":"Maiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shrikanth K.","family":"Venkatachalagupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neethukrishna","family":"Kausthubham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanny","family":"Kort\u00fcm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Rau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Wey-Fabrizius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lotte","family":"Van Den Heuvel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josephina","family":"Meester","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lut","family":"Van Laer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anju","family":"Shukla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Loeys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katta M.","family":"Girisha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Kutsche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"80755_CR1","doi-asserted-by":"publisher","first-page":"582","DOI":"10.21037\/acs.2017.11.03","volume":"6","author":"JAN Meester","year":"2017","unstructured":"Meester, J. A. N. et al. Differences in manifestations of Marfan syndrome, Ehlers\u2013Danlos syndrome, and Loeys\u2013Dietz syndrome. Ann. Cardiothorac. Surg. 6, 582\u2013594. https:\/\/doi.org\/10.21037\/acs.2017.11.03 (2017).","journal-title":"Ann. Cardiothorac. Surg."},{"key":"80755_CR2","unstructured":"Dietz, H. C. Marfan Syndrome. In (eds Adam M. P. et al.) GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132020. 2001 Apr 18 [updated 2017 Oct 12]."},{"key":"80755_CR3","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/352337a0","volume":"352","author":"HC Dietz","year":"1991","unstructured":"Dietz, H. C. et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. 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Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders. Circulation 120, 2541\u20132549. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.109.887042 (2009).","journal-title":"Circulation"},{"key":"80755_CR7","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8122079","author":"K M\u00fchlst\u00e4dt","year":"2019","unstructured":"M\u00fchlst\u00e4dt, K. et al. Case-matched comparison of cardiovascular outcome in Loeys\u2013Dietz Syndrome versus Marfan Syndrome. J. Clin. Med. https:\/\/doi.org\/10.3390\/jcm8122079 (2019).","journal-title":"J. Clin. Med."},{"key":"80755_CR8","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1002\/humu.22854","volume":"36","author":"D Micha","year":"2015","unstructured":"Micha, D. et al. SMAD2 mutations are associated with arterial aneurysms and dissections. Hum. Mutat. 36, 1145\u20131149. https:\/\/doi.org\/10.1002\/humu.22854 (2015).","journal-title":"Hum. 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A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat. Genet. 37, 275\u2013281. https:\/\/doi.org\/10.1038\/ng1511 (2005).","journal-title":"Nat. Genet."},{"key":"80755_CR14","unstructured":"Greally, M. T. Shprintzen\u2013Goldberg Syndrome. In (eds M. P. Adam et al.). GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132020. 2006 Jan 13 [updated 2020 Apr 9]."},{"key":"80755_CR15","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/ejhg.2014.61","volume":"23","author":"D Schepers","year":"2015","unstructured":"Schepers, D. et al. The SMAD-binding domain of SKI: A hotspot for de novo mutations causing Shprintzen\u2013Goldberg syndrome. Eur. J. Hum. Genet. 23, 224\u2013228. https:\/\/doi.org\/10.1038\/ejhg.2014.61 (2015).","journal-title":"Eur. J. Hum. 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