SPEAKER PRESENTATION Open Access Next generation diagnostics on cardiomyopathy Jean-Louis Blouin 1,2* , Jeremy Bevillard 2 , Periklis Makrythanasis 2 , Michel Guipponi 1,2 , Federico Santoni 2 , Stylianos E. Antonarakis 1,2 , Siv Fokstuen 1 From International Conference on Human Genetics and 39th Annual Meeting of the Indian Society of Human Genetics (ISHG) Ahmadabad, India. 23-25 January 2013 Cardiomyopathies are common, seemingly monogenic autosomal dominant cardiac disorders known as the pri- mary cause of sudden cardiac death in young adults. These diseases are characterized by a remarkable genetic heterogeneity, which makes it difficult to unravel the causative mutation in a diagnostic laboratory that is very laborious and expensive by Sanger sequencing. To circumvent these limitations, we explored solutions of high throughput sequencing of targeted exomes with the aim to implement this approach in routine diagnostics. As a first test we designed a capture microarray with the total genomic length of 1 Mbp that includes all exons/splicing sites of 130 genes involved in cardiovas- cular mendelian disorders and analyzed simultaneously four samples by multiplexing patients with cardiomyopathies or Long-QT syndrome. Pathogenic mutations and variants of unknown significance were found thus resolving the genetic causes of the cardiopathy in three. In the fourth patient the mutation usually associated with hypertrophic cardiomyopathy was found with Long-QT. Further developments to next generation diagnostics are now in progress, and will be also discussed. In conclusion, high throughput sequencing holds con- siderable promises for molecular diagnosis of highly het- erogeneous disorders in clinical practice and allows a better understanding of the complexity of mendelian disorders. Authors’ details 1 Genetic Medicine, University Hospitals of Geneva, Switzerland. 2 Genetic Medicine and Development, University of Geneva School of Medicine, Switzerland. Published: 21 January 2014 doi:10.1186/1755-8166-7-S1-I4 Cite this article as: Blouin et al.: Next generation diagnostics on cardiomyopathy. Molecular Cytogenetics 2014 7(Suppl 1):I4. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color ﬁgure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit * Correspondence: [email protected] 1 Genetic Medicine, University Hospitals of Geneva, Switzerland Full list of author information is available at the end of the article Blouin et al. Molecular Cytogenetics 2014, 7(Suppl 1):I4 http://www.molecularcytogenetics.org/content/7/S1/I4 © 2014 Blouin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Page 1: Next generation diagnostics on cardiomyopathy

SPEAKER PRESENTATION Open Access

Next generation diagnostics on cardiomyopathyJean-Louis Blouin1,2*, Jeremy Bevillard2, Periklis Makrythanasis2, Michel Guipponi1,2, Federico Santoni2,Stylianos E. Antonarakis1,2, Siv Fokstuen1

From International Conference on Human Genetics and 39th Annual Meeting of the Indian Society ofHuman Genetics (ISHG)Ahmadabad, India. 23-25 January 2013

Cardiomyopathies are common, seemingly monogenicautosomal dominant cardiac disorders known as the pri-mary cause of sudden cardiac death in young adults.These diseases are characterized by a remarkable geneticheterogeneity, which makes it difficult to unravel thecausative mutation in a diagnostic laboratory that is verylaborious and expensive by Sanger sequencing.To circumvent these limitations, we explored solutions

of high throughput sequencing of targeted exomes withthe aim to implement this approach in routine diagnos-tics. As a first test we designed a capture microarraywith the total genomic length of 1 Mbp that includes allexons/splicing sites of 130 genes involved in cardiovas-cular mendelian disorders and analyzed simultaneouslyfour samples by multiplexing patients with cardiomyo-pathies or Long-QT syndrome. Pathogenic mutationsand variants of unknown significance were found thusresolving the genetic causes of the cardiopathy in three.In the fourth patient the mutation usually associatedwith hypertrophic cardiomyopathy was found withLong-QT. Further developments to next generationdiagnostics are now in progress, and will be alsodiscussed.In conclusion, high throughput sequencing holds con-

siderable promises for molecular diagnosis of highly het-erogeneous disorders in clinical practice and allows abetter understanding of the complexity of mendeliandisorders.

Authors’ details1Genetic Medicine, University Hospitals of Geneva, Switzerland. 2GeneticMedicine and Development, University of Geneva School of Medicine,Switzerland.

Published: 21 January 2014

doi:10.1186/1755-8166-7-S1-I4Cite this article as: Blouin et al.: Next generation diagnostics oncardiomyopathy. Molecular Cytogenetics 2014 7(Suppl 1):I4.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

* Correspondence: [email protected] Medicine, University Hospitals of Geneva, SwitzerlandFull list of author information is available at the end of the article

Blouin et al. Molecular Cytogenetics 2014, 7(Suppl 1):I4http://www.molecularcytogenetics.org/content/7/S1/I4

© 2014 Blouin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

mailto:[email protected]

http://creativecommons.org/licenses/by/2.0

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