Marfan Syndrome Caused by Disruption of the <i>FBN1</i> Gene due to A Reciprocal Chromosome Translocation

Marfan syndrome (MFS) is a hereditary connective tissue disease caused by heterozygous mutations in the fibrillin-1 gene (<i>FBN1</i>) located on chromosome 15q21.1. A complex chromosomal rearrangement leading to MFS has only been reported in one case so far. We report on a mother and da...

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Autores principales:	Anna Clara Schnause, Katalin Komlosi, Barbara Herr, Jürgen Neesen, Paul Dremsek, Thomas Schwarz, Andreas Tzschach, Sabine Jägle, Ekkehart Lausch, Judith Fischer, Birgitta Gläser
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>FBN1</i> Marfan syndrome apparently balanced chromosomal rearrangements (ABCR) optical genome mapping (OGM) gene disruption Genetics QH426-470
Acceso en línea:	https://doaj.org/article/420d3776f61b410daa13a92f8140dc7b
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spelling	oai:doaj.org-article:420d3776f61b410daa13a92f8140dc7b2021-11-25T17:42:33ZMarfan Syndrome Caused by Disruption of the <i>FBN1</i> Gene due to A Reciprocal Chromosome Translocation10.3390/genes121118362073-4425https://doaj.org/article/420d3776f61b410daa13a92f8140dc7b2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1836https://doaj.org/toc/2073-4425Marfan syndrome (MFS) is a hereditary connective tissue disease caused by heterozygous mutations in the fibrillin-1 gene (<i>FBN1</i>) located on chromosome 15q21.1. A complex chromosomal rearrangement leading to MFS has only been reported in one case so far. We report on a mother and daughter with marfanoid habitus and no pathogenic variant in the <i>FBN1</i> gene after next generation sequencing (NGS) analysis, both showing a cytogenetically reciprocal balanced translocation between chromosomes 2 and 15. By means of fluorescence in situ hybridization of Bacterial artificial chromosome (BAC) clones from the breakpoint area on chromosome 15 the breakpoint was narrowed down to a region of approximately 110 kb in <i>FBN1</i>. With the help of optical genome mapping (OGM), the translocation breakpoints were further refined on chromosomes 2 and 15. Sequencing of the regions affected by the translocation identified the breakpoint of chromosome 2 as well as the breakpoint of chromosome 15 in the <i>FBN1</i> gene leading to its disruption. To our knowledge, this is the first report of patients with typical clinical features of MFS showing a cytogenetically reciprocal translocation involving the <i>FBN1</i> gene. Our case highlights the importance of structural genome variants as an underlying cause of monogenic diseases and the useful clinical application of OGM in the elucidation of structural variants.Anna Clara SchnauseKatalin KomlosiBarbara HerrJürgen NeesenPaul DremsekThomas SchwarzAndreas TzschachSabine JägleEkkehart LauschJudith FischerBirgitta GläserMDPI AGarticle<i>FBN1</i>Marfan syndromeapparently balanced chromosomal rearrangements (ABCR)optical genome mapping (OGM)gene disruptionGeneticsQH426-470ENGenes, Vol 12, Iss 1836, p 1836 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>FBN1</i> Marfan syndrome apparently balanced chromosomal rearrangements (ABCR) optical genome mapping (OGM) gene disruption Genetics QH426-470
spellingShingle	<i>FBN1</i> Marfan syndrome apparently balanced chromosomal rearrangements (ABCR) optical genome mapping (OGM) gene disruption Genetics QH426-470 Anna Clara Schnause Katalin Komlosi Barbara Herr Jürgen Neesen Paul Dremsek Thomas Schwarz Andreas Tzschach Sabine Jägle Ekkehart Lausch Judith Fischer Birgitta Gläser Marfan Syndrome Caused by Disruption of the <i>FBN1</i> Gene due to A Reciprocal Chromosome Translocation
description	Marfan syndrome (MFS) is a hereditary connective tissue disease caused by heterozygous mutations in the fibrillin-1 gene (<i>FBN1</i>) located on chromosome 15q21.1. A complex chromosomal rearrangement leading to MFS has only been reported in one case so far. We report on a mother and daughter with marfanoid habitus and no pathogenic variant in the <i>FBN1</i> gene after next generation sequencing (NGS) analysis, both showing a cytogenetically reciprocal balanced translocation between chromosomes 2 and 15. By means of fluorescence in situ hybridization of Bacterial artificial chromosome (BAC) clones from the breakpoint area on chromosome 15 the breakpoint was narrowed down to a region of approximately 110 kb in <i>FBN1</i>. With the help of optical genome mapping (OGM), the translocation breakpoints were further refined on chromosomes 2 and 15. Sequencing of the regions affected by the translocation identified the breakpoint of chromosome 2 as well as the breakpoint of chromosome 15 in the <i>FBN1</i> gene leading to its disruption. To our knowledge, this is the first report of patients with typical clinical features of MFS showing a cytogenetically reciprocal translocation involving the <i>FBN1</i> gene. Our case highlights the importance of structural genome variants as an underlying cause of monogenic diseases and the useful clinical application of OGM in the elucidation of structural variants.
format	article
author	Anna Clara Schnause Katalin Komlosi Barbara Herr Jürgen Neesen Paul Dremsek Thomas Schwarz Andreas Tzschach Sabine Jägle Ekkehart Lausch Judith Fischer Birgitta Gläser
author_facet	Anna Clara Schnause Katalin Komlosi Barbara Herr Jürgen Neesen Paul Dremsek Thomas Schwarz Andreas Tzschach Sabine Jägle Ekkehart Lausch Judith Fischer Birgitta Gläser
author_sort	Anna Clara Schnause
title	Marfan Syndrome Caused by Disruption of the <i>FBN1</i> Gene due to A Reciprocal Chromosome Translocation
title_short	Marfan Syndrome Caused by Disruption of the <i>FBN1</i> Gene due to A Reciprocal Chromosome Translocation
title_full	Marfan Syndrome Caused by Disruption of the <i>FBN1</i> Gene due to A Reciprocal Chromosome Translocation
title_fullStr	Marfan Syndrome Caused by Disruption of the <i>FBN1</i> Gene due to A Reciprocal Chromosome Translocation
title_full_unstemmed	Marfan Syndrome Caused by Disruption of the <i>FBN1</i> Gene due to A Reciprocal Chromosome Translocation
title_sort	marfan syndrome caused by disruption of the <i>fbn1</i> gene due to a reciprocal chromosome translocation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/420d3776f61b410daa13a92f8140dc7b
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Marfan Syndrome Caused by Disruption of the <i>FBN1</i> Gene due to A Reciprocal Chromosome Translocation

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