TY - JOUR
T1 - Autosomal dominant Marfan syndrome caused by a previously reported recessive FBN1 variant
AU - Overwater, Eline
AU - Efrat, Rifka
AU - Barge-Schaapveld, Daniela Q. C. M.
AU - Lakeman, Phillis
AU - Weiss, Marjan M.
AU - Maugeri, Alessandra
AU - van Tintelen, J. Peter
AU - Houweling, Arjan C.
PY - 2019/2
Y1 - 2019/2
N2 - Background: Pathogenic variants in FBN1 cause autosomal dominant Marfan syndrome but can also be found in patients presenting with apparently isolated features of Marfan syndrome. Moreover, several families with autosomal recessive Marfan syndrome caused by pathogenic variants in FBN1 have been described. The aim of this report was to underline the clinical variability that can be associated with the pathogenic variant c.1453C>T, p.(Arg485Cys) in FBN1. Methods: We provide the clinical details of two autosomal dominant families with this specific FBN1 variant, which was previously associated with autosomal recessive Marfan syndrome. Results: Clinical data of 14 individuals carrying this variant from these two families were collected retrospectively. In both families, the diagnosis of autosomal dominant Marfan syndrome was established based on the characteristics of the variant and the phenotype which includes aortic aneurysms and dissections. Of interest, in one of the families, multiple relatives were diagnosed with early onset abdominal aortic aneurysms. Conclusion: In conclusion, FBN1 variant c.1453C>T, p.(Arg485Cys) is a pathogenic variant that can cause autosomal dominant Marfan syndrome characterized by a high degree of clinical variability and apparently isolated early onset familial abdominal aortic aneurysms.
AB - Background: Pathogenic variants in FBN1 cause autosomal dominant Marfan syndrome but can also be found in patients presenting with apparently isolated features of Marfan syndrome. Moreover, several families with autosomal recessive Marfan syndrome caused by pathogenic variants in FBN1 have been described. The aim of this report was to underline the clinical variability that can be associated with the pathogenic variant c.1453C>T, p.(Arg485Cys) in FBN1. Methods: We provide the clinical details of two autosomal dominant families with this specific FBN1 variant, which was previously associated with autosomal recessive Marfan syndrome. Results: Clinical data of 14 individuals carrying this variant from these two families were collected retrospectively. In both families, the diagnosis of autosomal dominant Marfan syndrome was established based on the characteristics of the variant and the phenotype which includes aortic aneurysms and dissections. Of interest, in one of the families, multiple relatives were diagnosed with early onset abdominal aortic aneurysms. Conclusion: In conclusion, FBN1 variant c.1453C>T, p.(Arg485Cys) is a pathogenic variant that can cause autosomal dominant Marfan syndrome characterized by a high degree of clinical variability and apparently isolated early onset familial abdominal aortic aneurysms.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062152672&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30485715
U2 - https://doi.org/10.1002/mgg3.518
DO - https://doi.org/10.1002/mgg3.518
M3 - Article
C2 - 30485715
SN - 2324-9269
VL - 7
JO - Molecular genetics and genomic medicine
JF - Molecular genetics and genomic medicine
IS - 2
M1 - e00518
ER -