Skip to main content
main-content

01.12.2018 | Research | Ausgabe 1/2018 Open Access

Journal of Translational Medicine 1/2018

Molecular analysis of inherited cardiomyopathy using next generation semiconductor sequencing technologies

Zeitschrift:
Journal of Translational Medicine > Ausgabe 1/2018
Autoren:
Chaoxia Lu, Wei Wu, Fang Liu, Kunqi Yang, Jiacheng Li, Yaping Liu, Rongrong Wang, Nuo Si, Peng Gao, Yongtai Liu, Shuyang Zhang, Xue Zhang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12967-018-1605-5) contains supplementary material, which is available to authorized users.
Chaoxia Lu, Wei Wu, Shuyang Zhang and Xue Zhang contributed equally to this work

Abstract

Background

Cardiomyopathies are the most common clinical and genetic heterogeneity cardiac diseases, and genetic contribution in particular plays a major role in patients with primary cardiomyopathies. The aim of this study is to investigate cases of inherited cardiomyopathy (IC) for potential disease-causing mutations in 64 genes reported to be associated with IC.

Methods

A total of 110 independent cases or families diagnosed with various primary cardiomyopathies, including hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular non-compaction, and undefined cardiomyopathy, were collected after informed consent. A custom designed panel, including 64 genes, was screened using next generation sequencing on the Ion Torrent PGM platform. The best candidate disease-causing variants were verified by Sanger sequencing.

Results

A total of 78 variants in 73 patients were identified. After excluding the variants predicted to be benign and VUS, 26 pathogenic or likely pathogenic variants were verified in 26 probands (23.6%), including a homozygous variant in the SLC25A4 gene. Of these variants, 15 have been reported in the Human Gene Mutation Database or ClinVar database, while 11 are novel. The majority of variants were observed in the MYH7 (8/26) and MYBPC3 (6/26) gene. Titin (TTN) truncating mutations account for 13% in our dilated cardiomyopathy cases (3/23).

Conclusions

This study provides an overview of the genetic aberrations in this cohort of Chinese IC patients and demonstrates the power of next generation sequencing in IC. Genetic results can provide precise clinical diagnosis and guidance regarding medical care for some individuals.
Zusatzmaterial
Additional file 1: Table S1. List of the genes selected to perform the custom panel design.
Additional file 2: Figure S1. Variant filtration workflow.
Additional file 3: Table S2. List of variant annotation information.
Additional file 4: Table S3. Clinical characteristics of the patients with positive variants.
Additional file 5: Table S4. Variants of uncertain significance or benign identified by cardiomyopathy NGS panels in this study.
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2018

Journal of Translational Medicine 1/2018 Zur Ausgabe