Genomic analysis of a novel pathogenic variant in the gene LMNA associated with cardiac laminopathies found in Ecuadorian siblings: A case report

Guevara-Ramí­rez, Patricia; Cadena-Ullauri, Santiago; Ibarra-Castillo, Rita; Laso-Bayas, José Luis; Paz-Cruz, Elius; Tamayo-Trujillo, Rafael; Ruiz-Pozo, Viviana A.; Doménech, Nieves; Ibarra-Rodríguez, Adriana Alexandra; Zambrano, Ana Karina

doi:10.3389/fcvm.2023.1141083

Cited by 4 publications

(4 citation statements)

References 27 publications

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“…However, we could not evaluate the genomic data of the proband's family, therefore we are not able to determine if this pathogenic variant is inherited. In Ecuador, few studies have reported ancestry analyses and cardiovascular diseases (Cadena-Ullauri et al, 2022;Guevara-Ramírez et al, 2023). In the present case report, the proband shows a high European proportion (40.3%) in ancestry proportion analysis.…”

Section: Diagnostic Assessmentsupporting

confidence: 42%

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Identifying genomic variant associated with long QT syndrome type 2 in an ecuadorian mestizo individual: a case report

Tamayo-Trujillo,

Ibarra-Castillo,

Laso-Bayas

et al. 2024

Front. Genet.

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IntroductionLong QT syndrome (LQTS) is an autosomal dominant inherited cardiac condition characterized by a QT interval prolongation and risk of sudden death. There are 17 subtypes of this syndrome associated with genetic variants in 11 genes. The second most common is type 2, caused by a mutation in the KCNH2 gene, which is part of the potassium channel and influences the final repolarization of the ventricular action potential. This case report presents an Ecuadorian teen with congenital Long QT Syndrome type 2 (OMIM ID: 613688), from a family without cardiac diseases or sudden cardiac death backgrounds.Case presentationA 14-year-old girl with syncope, normal echocardiogram, and an irregular electrocardiogram was diagnosed with LQTS. Moreover, by performing Next-Generation Sequencing, a pathogenic variant in the KCNH2 gene p.(Ala614Val) (ClinVar ID: VCV000029777.14) associated with LQTS type 2, and two variants of uncertain significance in the AKAP9 p.(Arg1654GlyfsTer23) (rs779447911), and TTN p. (Arg34653Cys) (ClinVar ID: VCV001475968.4) genes were identified. Furthermore, ancestry analysis showed a mainly Native American proportion.ConclusionBased on the genomic results, the patient was identified to have a high-risk profile, and an implantable cardioverter defibrillator was selected as the best treatment option, highlighting the importance of including both the clinical and genomics aspects for an integral diagnosis.

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Section: Diagnostic Assessmentsupporting

confidence: 42%

“…In Ecuador, few studies have reported ancestry analyses and cardiovascular diseases ( Cadena-Ullauri et al, 2022 ; Guevara-Ramírez et al, 2023 ). In the present case report, the proband shows a high European proportion (40.3%) in ancestry proportion analysis.…”

Section: Discussionmentioning

confidence: 99%

Identifying genomic variant associated with long QT syndrome type 2 in an ecuadorian mestizo individual: a case report

Tamayo-Trujillo,

Ibarra-Castillo,

Laso-Bayas

et al. 2024

Front. Genet.

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“…Furthermore, by identifying mutations associated with CVDs, NGS facilitates early diagnosis, personalized pharmacological approaches, and identification of novel biomarkers. Thus, NGS is a valuable tool in CVD management [ 7 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, such studies are limited in Ecuador, a low- and middle-income country. Only a few studies have been conducted, yielding interesting results related to the Ecuadorian population [ 7 - 9 ]. Several challenges contribute to this gap, encompassing economic, infrastructural, and educational obstacles.…”

Section: Introductionmentioning

confidence: 99%

Exploring Atrial Fibrillation: Understanding the Complex Relation Between Lifestyle and Genetic Factors

Tamayo-Trujillo,

Paz-Cruz,

Cadena-Ullauri

et al. 2024

J Med Cases

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Cardiovascular diseases (CVDs) are the leading cause of death worldwide across diverse ethnic groups. Among these, atrial fibrillation (AF) stands as one of the most prevalent types of arrhythmias and the primary cause of stroke. Risk factors associated with AF include alcohol consumption, aging, high blood pressure, hypertension, inflammation, and genetic factors. A family history of CVD could indicate an increased risk. Consequently, genetic, and genomic testing should be performed to identify the molecular etiology of CVDs and assess at-risk patients. It is important to note that CVDs are the results of the complex interplay of genes and environmental factors, including ethnicity. In this case, the proband’s clinic story includes a history of smoking abuse for 10 years (10 cigarettes per day), obesity, hypertension, and an associated familial history. These risk factors, along with genetic variants, could trigger the early onset of AF. In recent years, genetic and genomic studies have significantly advanced our understanding of CVD etiology, given that next-generation sequencing (NGS) allows for the identification of genetic variants that could contribute to these pathologies. Furthermore, NGS facilitates early diagnosis, personalized pharmacological approaches, and identification of novel biomarkers. Thus, NGS is a valuable tool in CVD management. However, such studies are limited in Ecuador, a low- and middle-income country. Several challenges contribute to this gap, encompassing economic, infrastructural, and educational obstacles. Notably, the cost of genetic and genomic studies may also pose a barrier, restricting access to a portion of the population. In this case report, we present a 56-year-old Ecuadorian woman, who has been diagnosed with AF; however, after performing NGS no disease-associated variants were found, despite having strong clinical signs and symptoms. In summary, this case report contributes valuable insights into the complex interplay between genetic and lifestyle factors in the development and management of AF. The case report aims to underscore the potential impact of genetic variants on disease risk, even when classified as variants of uncertain significance, and the importance of an integral approach to patient care that includes genetic screening, lifestyle interventions, and tailored pharmacological treatment.

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The Autosomal Short Tandem Repeat Polymorphisms Are Potentially Associated with Cardiovascular Disease Predisposition in the Latin American Population: A Mini Review

Zambrano,

Cadena-Ullauri,

Guevara-Ramírez

et al. 2023

BioMed Research International

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According to the World Health Organization, cardiovascular diseases (CVDs) are the leading cause of death worldwide across nearly all ethnic groups. Inherited cardiac conditions comprise a wide spectrum of diseases that affect the heart, including abnormal structural features and functional impairments. In Latin America, CVDs are the leading cause of death within the region. Factors such as population aging, unhealthy diet, obesity, smoking, and a sedentary lifestyle have increased the risk of CVD. The Latin American population is characterized by its diverse ethnic composition with varying percentages of each ancestral component (African, European, and Native American ancestry). Short tandem repeats (STRs) are DNA sequences with 2-6 base pair repetitions and constitute ~3% of the human genome. Importantly, significant allele frequency variations exist between different populations. While studies have described that STRs are in noncoding regions of the DNA, increasing evidence suggests that simple sequence repeat variations may be critical for proper gene activity and regulation. Furthermore, several STRs have been identified as potential disease predisposition markers. The present review is aimed at comparing and describing the frequencies of autosomal STR polymorphisms potentially associated with cardiovascular disease predisposition in Latin America compared with other populations.

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Genomic analysis of a novel pathogenic variant in the gene LMNA associated with cardiac laminopathies found in Ecuadorian siblings: A case report

Cited by 4 publications

References 27 publications

Identifying genomic variant associated with long QT syndrome type 2 in an ecuadorian mestizo individual: a case report

Identifying genomic variant associated with long QT syndrome type 2 in an ecuadorian mestizo individual: a case report

Exploring Atrial Fibrillation: Understanding the Complex Relation Between Lifestyle and Genetic Factors

The Autosomal Short Tandem Repeat Polymorphisms Are Potentially Associated with Cardiovascular Disease Predisposition in the Latin American Population: A Mini Review

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