Hungarian Marfan family with large FBN1 deletion calls attention to copy number variation detection in the current NGS era

Kálmán Benke; Bence Ágg; Janine Meienberg; Anna M Kopps; Nathalie Fattorini; Roland Stengl; Noémi Daradics; Miklós Pólos; András Bors; Tamás Radovits; Béla Merkely; Julie De Backer; Zoltán Szabolcs; Gábor Mátyás

doi:10.21037/jtd.2018.04.40

Hungarian Marfan family with large FBN1 deletion calls attention to copy number variation detection in the current NGS era

J Thorac Dis. 2018 Apr;10(4):2456-2460. doi: 10.21037/jtd.2018.04.40.

Authors

Kálmán Benke^{1

2}, Bence Ágg^{1

2

3}, Janine Meienberg⁴, Anna M Kopps⁴, Nathalie Fattorini⁴, Roland Stengl^{1

2}, Noémi Daradics^{1

2}, Miklós Pólos^{1

2}, András Bors⁵, Tamás Radovits¹, Béla Merkely¹, Julie De Backer⁶, Zoltán Szabolcs^{1

2}, Gábor Mátyás^{4

7}

Affiliations

¹ Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
² Hungarian Marfan Foundation, Budapest, Hungary.
³ Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
⁴ Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich, Switzerland.
⁵ Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest, Hungary.
⁶ Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium.
⁷ Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.

Abstract

Copy number variations (CNVs) comprise about 10% of reported disease-causing mutations in Mendelian disorders. Nevertheless, pathogenic CNVs may have been under-detected due to the lack or insufficient use of appropriate detection methods. In this report, on the example of the diagnostic odyssey of a patient with Marfan syndrome (MFS) harboring a hitherto unreported 32-kb FBN1 deletion, we highlight the need for and the feasibility of testing for CNVs (>1 kb) in Mendelian disorders in the current next-generation sequencing (NGS) era.

Keywords: Copy number variations (CNVs); FBN1 gene; Marfan syndrome (MFS); genetic testing; whole-genome sequencing (WGS).