Whole exome sequencing identifies a novel mutation (c.333 + 2T &gt; C) of TNNI3K in a Chinese family with dilated cardiomyopathy and cardiac conduction disease

Fan, Liang‐Liang; Huang, Hao; Jin, Jie‐Yuan; Li, Jingjing; Chen, Yaqin; Zhao, Shui‐Ping; Xiang, Rong

doi:10.1016/j.gene.2018.01.055

Cited by 26 publications

(34 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2,3 More recent studies on cohorts of patients with CA/ DD/ID have documented diagnostic yields ranging from 16% to 28%. [4][5][6] As a result, CMA is a well-established tool in clinical practice, yet this testing will not capture singlenucleotide variations (SNVs) or small insertion/deletions (indels), smaller structural variants, and other pathogenic variant types contributing to CA/DD/ID.…”

Section: Introductionmentioning

confidence: 99%

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability

Malinowski¹,

Miller

Demmer

et al. 2020

Genetics in Medicine

View full text Add to dashboard Cite

A full list of authors and affiliations appears at the end of the paper.Disclaimer: The ACMG has recruited expert panels, chosen for their scientific and clinical expertise, to conduct systematic evidence reviews (SERs) to support the development of clinical practice guidelines. An SER focuses on a specific scientific question and then identifies, analyzes and summarizes the findings of relevant studies. ACMG SERs are provided primarily as educational resources for medical geneticists and other clinicians to help them provide quality medical services. They should not be considered inclusive of all relevant information on the topic reviewed. Reliance on this SER is completely voluntary and does not necessarily assure a successful medical outcome. In determining the propriety of any specific procedure or test, the clinician should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. Clinicians are encouraged to document the reasons for the use of a particular procedure or test, whether or not it is in conformance with this SER. Clinicians also are advised to take notice of the date this SER was published, and to consider other medical and scientific information that becomes available after that date.

show abstract

Section: Introductionmentioning

confidence: 99%

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability

Malinowski¹,

Miller

Demmer

et al. 2020

Genetics in Medicine

View full text Add to dashboard Cite

show abstract

“…The mutation identified in the proband was absent in all available healthy relatives included in this study, but unfortunately it was not tested in the two deceased symptomatic relatives (father and paternal grandfather). This new mutation (p.R541W), resulting in a substitution of arginine by tryptophan, was located in a highly evolutionarily conserved site ( Figure 1F) and was also absent in our 200 local control subjects (Fan et al, 2018). A previous in vitro study proved that this mutation (p.R541W) may substantially impaire inactivation by antithrombin, resulting in a prolonged clotting function and leading to an ATR phenotype, which further proved that the mutation may be a high risk factor for thrombosis (Tamura et al, 2017).…”

Section: Mutation Validation and Co-segregation Analysismentioning

confidence: 69%

A Novel Heterozygous Variant in F2 Gene in a Chinese Patient With Coronary Thrombosis and Acute Myocardial Infarction Leads to Antithrombin Resistance

et al. 2020

Self Cite

View full text Add to dashboard Cite

Thrombophilia refers to a group of conditions where the blood clots more easily than normal. These blood clots can cause problems such as deep vein thrombosis or pulmonary embolism. Most kinds of mutated coagulation factors II (F2) exhibit lower procoagulant activity, but in some cases, a higher coagulation rate has been observed. The underlying mechanism is that those variations can prevent F2s from being inhibited by antithrombin, leading to a contiguous activation of procoagulation, and causing recurrent thromboembolism. In this study, a patient was admitted to our hospital due to repeated chest pain for 2 days and aggravated for 4 h. A medical history investigation showed that he had three deep venous thromboses in the lower limbs and one portal vein thrombosis events during the past 10 years. The electrocardiogram showed Q wave elevation and slight ST segment elevation in lead V2, and coronary angiogram showed a total occlusion of the left anterior descending artery. Laboratory testing found that troponin I was obviously elevated. Family history also indicated that both his father (II-3) and grandfather (I-1) died from pulmonary thromboembolism. Whole-exome sequencing was performed to detect the genetic lesion of the patient, and a novel mutation (c.1621 C>T/p.R541W) of F2 was identified in the patient. This novel mutation resulted in a substitution of arginine by tryptophan, leading to antithrombin resistance (ATR). Our study is consistent with previously published papers. In conclusion, this study not only identifies a novel mutation of F2 and will contribute to the genetic diagnosis and counseling of families with thrombosis but also suggests that the site p.R541 of F2 may play a crucial role in thrombosis.

show abstract

“…This mutation results in the early appearance of stop codon which is anticipated to produce truncated protein lacking partial protein kinase domain along with the C-terminus. For all we know, a premature termination TA B L E 3 Comparison of clinical presentation of cases with TNNI3K mutation Theis, et al (2014) 16 Xi, et al (2015) 17 Fan, et al (2018) 18 Podliesna, et al (2019) 19 Podliesna, et al (2019) 19 Podliesna, codon (PTC) may result in loss of function (LOF) through NMD. 23,24 NMD refers to rapid degradation of mRNAs in transcripts harboring a PTC existing in all eukaryotic cells, which prevents the synthesis of truncated and potentially toxic proteins.…”

Section: Discussionmentioning

confidence: 99%

Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease

Liu

et al. 2020

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background Cardiac conduction disease (CCD) is a common cardiovascular disease which can lead to life‐threatening conditions. The importance of heredity in CCD has been realized in recent years. Several causal genes have been found to be implicated in CCD such as SCN5A, TRPM4, SCN1B, TNNI3K, LMNA, and NKX2.5. To date, only four genetic mutations in TNNI3K have been identified related to CCD. Methods Whole‐exome sequencing (WES) was carried out in order to identify the underlying disease‐causing mutation in a Chinese family with CCD. The potential mutations were confirmed by Sanger sequencing. Real‐time qPCR was used to detect the level of TNNI3K mRNA expression. Results A nonsense mutation in TNNI3K (NM_015978.2: g.170891C > T, c.1441C > T) was identified in this family and validated by Sanger sequencing. Real‐time qPCR confirmed that the level of TNNI3K mRNA expression was decreased compared with the controls. Conclusions This study found the first nonsense TNNI3K mutation associated with CCD in a Chinese family. TNNI3K harboring the mutation (c.1441C > T) implicated a loss‐of‐function pathogenic mechanism with an autosomal dominant inheritance pattern. This research enriches the phenotypic spectrum of TNNI3K mutations, casting a new light upon the genotype‐phenotype correlations between TNNI3K mutations and CCD and indicating the importance of TNNI3K screening in CCD patients.

show abstract

Whole exome sequencing identifies a novel mutation (c.333 + 2T > C) of TNNI3K in a Chinese family with dilated cardiomyopathy and cardiac conduction disease

Cited by 26 publications

References 25 publications

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability

A Novel Heterozygous Variant in F2 Gene in a Chinese Patient With Coronary Thrombosis and Acute Myocardial Infarction Leads to Antithrombin Resistance

Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease

Contact Info

Product

Resources

About

Whole exome sequencing identifies a novel mutation (c.333 + 2T > C) of TNNI3K in a Chinese family with dilated cardiomyopathy and cardiac conduction disease

Cited by 26 publications

References 25 publications

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability

A Novel Heterozygous Variant in F2 Gene in a Chinese Patient With Coronary Thrombosis and Acute Myocardial Infarction Leads to Antithrombin Resistance

Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease

Contact Info

Product

Resources

About

Whole exome sequencing identifies a novel mutation (c.333 + 2T > C) of TNNI3K in a Chinese family with dilated cardiomyopathy and cardiac conduction disease