Multiplex targeted high-throughput sequencing for Mendelian cardiac disorders.

Details

Serval ID
serval:BIB_EF428E0A4CED
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multiplex targeted high-throughput sequencing for Mendelian cardiac disorders.
Journal
Clinical Genetics
Author(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
Publication state
Published
Issued date
2014
Volume
85
Number
4
Pages
365-370
Language
english
Abstract
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
Create date
11/04/2014 17:37
Last modification date
28/02/2020 11:49
Usage data