Multiplex targeted high-throughput sequencing for Mendelian cardiac disorders.

Détails

ID Serval
serval:BIB_EF428E0A4CED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Multiplex targeted high-throughput sequencing for Mendelian cardiac disorders.
Périodique
Clinical Genetics
Auteur(s)
Fokstuen S., Makrythanasis P., Nikolaev S., Santoni F., Robyr D., Munoz A., Bevillard J., Farinelli L., Iseli C., Antonarakis S.E., Blouin J.L.
ISSN
1399-0004 (Electronic)
ISSN-L
0009-9163
Statut éditorial
Publié
Date de publication
2014
Volume
85
Numéro
4
Pages
365-370
Langue
anglais
Résumé
Mendelian cardiomyopathies and arrhythmias are characterized by an important genetic heterogeneity, rendering Sanger sequencing very laborious and expensive. As a proof of concept, we explored multiplex targeted high-throughput sequencing (HTS) as a fast and cost-efficient diagnostic method for individuals suffering from Mendelian cardiac disorders. We designed a DNA capture assay including all exons from 130 genes involved in cardiovascular Mendelian disorders and analysed simultaneously four samples by multiplexing. Two patients had familial hypertrophic cardiomyopathy (HCM) and two patients suffered from long QT syndrome (LQTS). In patient 1 with HCM, we identified two known pathogenic missense variants in the two most frequently mutated sarcomeric genes MYH7 and MYBPC. In patient 2 with HCM, a known acceptor splice site variant in MYBPC3 was found. In patient 3 with LQTS, two missense variants in the genes SCN5A and KCNQ were identified. Finally, in patient 4 with LQTS a known missense variant was found in MYBPC3, which is usually mutated in patients with cardiomyopathy. Our results showed that multiplex targeted HTS works as an efficient and cost-effective tool for molecular diagnosis of heterogeneous disorders in clinical practice and offers new insights in the pathogenesis of these complex diseases.
Pubmed
Web of science
Création de la notice
11/04/2014 18:37
Dernière modification de la notice
03/03/2018 22:34
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