TY - JOUR T1 - A systematic study and literature review of parental somatic mosaicism of <em>FBN1</em> pathogenic variants in Marfan syndrome JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2020-107604 SP - jmedgenet-2020-107604 AU - Paula Fernández-Álvarez AU - Marta Codina-Sola AU - Irene Valenzuela AU - Gisela Teixidó-Turá AU - Anna Cueto-González AU - Ida Paramonov AU - María Antolín AU - Fermina López-Grondona AU - Teresa Vendrell AU - Artur Evangelista AU - Elena García-Arumí AU - Eduardo F Tizzano Y1 - 2021/04/28 UR - http://jmg.bmj.com/content/early/2021/04/27/jmedgenet-2020-107604.abstract N2 - Background A proportion of de novo variants in patients affected by genetic disorders, particularly those with autosomal dominant (AD) inheritance, could be the consequence of somatic mosaicism in one of the progenitors. There is growing evidence that germline and somatic mosaicism are more common and play a greater role in genetic disorders than previously acknowledged. In Marfan syndrome (MFS), caused by pathogenic variants in the fibrillin-1 gene (FBN1) gene, approximately 25% of the disease-causing variants are reported as de novo. Only a few cases of parental mosaicism have been reported in MFS.Methods Employing an amplicon-based deep sequencing (ADS) method, we carried out a systematic analysis of 60 parents of 30 FBN1 positive, consecutive patients with MFS with an apparently de novo pathogenic variant.Results Out of the 60 parents studied (30 families), the majority (n=51, 85%) had a systemic score of 0, seven had a score of 1 and two a score of 2, all due to minor criteria common in the normal population. We detected two families with somatic mosaicism in one of the progenitors, with a rate of 6.6% (2/30) of apparently de novo cases.Conclusions The search for parental somatic mosaicism should be routinely implemented in de novo cases of MFS, to offer appropriate genetic and reproductive counselling as well as to reveal masked, isolated clinical signs of MFS in progenitors that may require specific follow-up.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. ER -