Two Novel Pathogenic FBN1 Variations and Their Phenotypic Relationship of Marfan Syndrome
Marfan syndrome is an autosomal dominant disease affecting connective tissue involving the ocular, skeletal systems with a prevalence of 1/5,000 to 1/10,000 cases. Especially cardiovascular system disorders (aortic root dilatation and enlargement of the pulmonary artery) may be life-threatening. We report here the genetic analysis results of three unrelated cases clinically diagnosed as Marfan syndrome. Deoxyribonucleic acid (DNA) was isolated from EDTA (ethylenediaminetetraacetic acid)-blood samples of the patients. A next-generation sequencing panel containing 15 genes including FBN1 was used to determine the underlying pathogenic variants of Marfan syndrome. Three different variations, NM_000138.4(FBN1):c.229G > A(p.Gly77Arg), NM_000138.4(FBN1):c.165–2A > G (novel), NM_000138.4(FBN1):c.399delC (p.Cys134ValfsTer8) (novel) were determined in our three cases referred with a prediagnosis of Marfan syndrome. Our study has confirmed the utility of molecular testing in Marfan syndrome to support clinical diagnosis. With an accurate diagnosis and genetic counseling for prognosis of patients and family testing, the prenatal diagnosis will be possible.
S.Y. made substantial contributions to conception and design and gave the final approval of the version to be published. S.D., E.I.A., M.D., and E.A. made substantial contributions to the analysis and interpretation of the data. H.G. was involved in the drafting of the manuscript or revising it critically for important intellectual content.
20 August 2020 (online)
© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).
Georg Thieme Verlag KG
Stuttgart · New York
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