Autosomal dominant Marfan syndrome caused by a previously reported recessive FBN1 variant

Eline Overwater, Rifka Efrat, Daniela Q C M Barge-Schaapveld, Phillis Lakeman, Marjan M Weiss, Alessandra Maugeri, J Peter van Tintelen, Arjan C Houweling

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
JournalMolecular Genetics and Genomic Medicine
DOIs
Publication statusE-pub ahead of print - 28 Nov 2018

Cite this

@article{3a372e2697524b75b0770d2d5ddd29a3,
title = "Autosomal dominant Marfan syndrome caused by a previously reported recessive FBN1 variant",
abstract = "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.",
author = "Eline Overwater and Rifka Efrat and Barge-Schaapveld, {Daniela Q C M} and Phillis Lakeman and Weiss, {Marjan M} and Alessandra Maugeri and {van Tintelen}, {J Peter} and Houweling, {Arjan C}",
note = "{\circledC} 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.",
year = "2018",
month = "11",
day = "28",
doi = "10.1002/mgg3.518",
language = "English",
journal = "Molecular Genetics and Genomic Medicine",
issn = "2324-9269",
publisher = "John Wiley and Sons Inc.",

}

Autosomal dominant Marfan syndrome caused by a previously reported recessive FBN1 variant. / Overwater, Eline; Efrat, Rifka; Barge-Schaapveld, Daniela Q C M; Lakeman, Phillis; Weiss, Marjan M; Maugeri, Alessandra; van Tintelen, J Peter; Houweling, Arjan C.

In: Molecular Genetics and Genomic Medicine, 28.11.2018.

Research output: Contribution to journalArticleAcademicpeer-review

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

N1 - © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

PY - 2018/11/28

Y1 - 2018/11/28

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.

U2 - 10.1002/mgg3.518

DO - 10.1002/mgg3.518

M3 - Article

JO - Molecular Genetics and Genomic Medicine

JF - Molecular Genetics and Genomic Medicine

SN - 2324-9269

ER -