• PDF / 1,877,913 Bytes
• 12 Pages / 595.276 x 790.866 pts Page_size
• 71 Downloads / 188 Views

DOWNLOAD

REPORT

ORIGINAL ARTICLE

Family‑Based Whole Genome Sequencing Identified Novel Variants in ABCA5 Gene in a Patient with Idiopathic Ventricular Tachycardia Zhanhui Du1 · Shan Kuang2,3 · Yong Li2,3 · Peng Han2,3 · Junnian Liu2,3,4 · Zhiwei Wang2,3 · Yingping Huang2,3 · Yuanning Guan2,3 · Xun Xu2,3,4 · Xin Liu2,3,4 · Santasree Banerjee2,3,4 · Silin Pan1 Received: 14 April 2020 / Accepted: 30 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Idiopathic ventricular tachycardia (IVT) is the major cause of sudden cardiac death. Patients with IVT were usually manifested without structural heart disease. In this present study, we performed family-based whole genome sequencing (WGS) and Sanger sequencing for a 5-year-old Chinese boy with IVT and all the unaffected family members in order to identify the candidate gene and disease-causing mutation underlying the disease phenotype. Results showed that a novel heterozygous single-nucleotide duplication (c.128dup) and a novel heterozygous missense (c.3328A > G) variant in ABCA5 gene were identified in the proband. The single-nucleotide duplication (c.128dupT), inherited from his father and patrilineal grandfather, leads to a frameshift which results into the formation of a truncated ABCA5 protein of 50 (p.Leu43Phefs*8) amino acids. Hence, it is a loss-of-function mutation. The missense (c.3328A > G) variant, inherited from his mother, leads to the replacement of isoleucine by valine at the position of 1110 (p.Ile1110Val) of the ABCA5 protein. Multiple sequence alignment showed that p.Ile1110 is evolutionarily conserved among several species indicating both the structural and functional significance of the p.Ile1110 residue in the wild-type ABCA5 protein. Quantitative RT-PCR showed that the ABCA5 mRNA expression levels were decreased in the proband. These two novel variants of ABCA5 gene were co-segregated well among all the members of this family. Our present study also strongly supports the importance of using family-based whole genome sequencing for identifying novel candidate genes associated with IVT. Keywords  Idiopathic ventricular tachycardia · ABCA5 gene · Novel mutation · Loss-of-function mutation · Family-based whole genome sequencing

Zhanhui Du, Shan Kuang and Yong Li contributed equally for this work. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0024​6-020-02446​-4) contains supplementary material, which is available to authorized users. * Santasree Banerjee [email protected] * Silin Pan [email protected] 1



Qingdao Women and Children’s Hospital, Qingdao University, Qingdao 266034, China

2



BGI‑Qingdao, BGI-Shenzhen, 2877 Tuanjie Road, Sino‑German Ecopark, Qingdao 266555, China

3

China National Gene Bank, BGI-Shenzhen, Shenzhen 518120, China

4

BGI-Shenzhen, Shenzhen 518083, China



Abbreviations IVT Idiopathic ventricular tachycardia WGS Whole genome sequencing WES Whole exome sequencing SNV Single-nucleotide variant INDEL Insertion/deletion CHD Conge

Recommend Documents

Novel variants in women with premature ovarian function decline identified via whole-exome sequencing

105 37 1MB

Whole genome sequencing identified a 16 kilobase deletion on ECA13 associated with distichiasis in Friesian horses

129 5 2MB

Pathogenic variants identified by whole-exome sequencing in 43 patients with epilepsy

181 78 514KB

Identification of single nucleotide variants in the Moroccan population by whole-genome sequencing

149 47 1MB

Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myocl

140 53 1MB

Whole exome sequencing highlights variants in association with Keratoconus in Jordanian families

125 84 627KB

Two novel likely pathogenic variants of HARS2 identified in a Chinese family with sensorineural hearing loss

151 34 2MB

Performance of copy number variants detection based on whole-genome sequencing by DNBSEQ platforms

162 115 1MB

Whole-exome sequencing identifies a novel mutation in spermine synthase gene (SMS) associated with Snyder-Robinson Syndr

99 88 1MB

Whole-exome sequencing in patients with protein aggregate myopathies reveals causative mutations associated with novel a

146 60 1MB

Whole-genome mining of abiotic stress gene loci in rice

190 63 4MB

The value of whole exome sequencing for genetic diagnosis in a patient with Bloom syndrome

136 5 739KB