Gestational Weight Gain: Is the Role of Genetic Variants a Determinant? A Review.

Excessive or insufficient gestational weight gain (GWG) leads to diverse adverse maternal and neonatal outcomes. There is evidence that pregestational body mass index (pBMI) plays a role in GWG, but no genetic cause has been identified. In this review, we aim to analyze genotype variants associated with GWG. Results: We identified seven genotype variants that may be involved in GWG regulation that were analyzed in studies carried out in Brazil, Romania, the USA, Turkey, Ukraine, and Canada. Some genetic variants were only associated with GWG in certain races or depending on the pBMI. In women who were obese or overweight before gestation, some genetic variants were associated with GWG. Environmental and genetic factors together showed a greater association with GWG than genetic factors alone; for example, type of diet was observed to have a significant influence. Conclusions: We found little scientific evidence of an association between genotype variants in countries with a high prevalence of women of reproductive age who are overweight and obese, such as in Latin America. GWG may be more dependent on environmental factors than genetic variants. We suggest a deeper study of genetic variants, cytokines, and their possible association with GWG, always with the respective control of potential cofounding factors, such as pBMI, diet, and race.

Niemann-Pick disease A or B in four pediatric patients and SMPD1 mutation carrier frequency in the Mexican population.

INTRODUCTION AND OBJECTIVES: Niemann-Pick disease type A (NPD-A) and B (NPD-B) are lysosomal storage diseases with a birth prevalence of 0.4-0.6/100,000. They are caused by a deficiency in acid sphingomyelinase, an enzyme encoded by SMPD1. We analyzed the phenotype and genotype of four unrelated Mexican patients, one with NPD-A and three with NPD-B. PATIENTS AND METHODS: Four female patients between 1 and 7 years of age were diagnosed with NPD-A or NPD-B by hepatosplenomegaly, among other clinical characteristics, and by determining the level of acid sphingomyelinase enzymatic activity and sequencing of the SMPD1 gene. Additionally, a 775bp amplicon of SMPD1 (from 11:6393835_6394609, including exons 5 and 6) was analyzed by capillary sequencing in a control group of 50 unrelated healthy Mexican Mestizos. RESULTS: An infrequent variant (c.1343A>G p.Tyr448Cys) was observed in two patients. One is the first NPD-A homozygous patient reported with this variant and the other a compound heterozygous NPD-B patient with the c.1829_1831delGCC p.Arg610del variant. Another compound heterozygous patient had the c.1547A>G p.His516Arg variant (not previously described in affected individuals) along with the c.1805G>A p.Arg602His variant. A new c.1263+8C>T pathogenic variant was encountered in a homozygous state in a NPD-B patient. Among the healthy control individuals there was a heterozygous carrier for the c.1550A>T (rs142787001) pathogenic variant, but none with the known pathogenic variants in the 11:6393835_6394609 region of SMPD1. CONCLUSIONS: The present study provides further NPD-A or B phenotype-genotype correlations. We detected a heterozygous carrier with a pathogenic variant in 1/50 healthy Mexican mestizos.

A Potential Association between Abdominal Obesity and the Efficacy of Humoral Immunity Induced by COVID-19 and by the AZD1222, Convidecia, BNT162b2, Sputnik V, and CoronaVac Vaccines.

Abdominal obesity is highly prevalent in Mexico and has a poor prognosis in terms of the severity of coronavirus disease (COVID-19) and low levels of antibodies induced by infection and vaccination. We evaluated the humoral immune response induced by COVID-19 and five different vaccination schedules in Mexican individuals with abdominal obesity and the effects of other variables. This prospective longitudinal cohort study included 2084 samples from 389 participants. The levels of anti-S1/S2 and anti-RBD IgG antibodies were measured at various time points after vaccination. A high prevalence of hospitalization and oxygen use was observed in individuals with abdominal obesity (AO) who had COVID-19 before vaccination; however, they also had high levels of anti-S1/S2 and anti-RBD-neutralizing IgG antibodies. The same was true for vaccination-induced antibody levels. However, their longevity was low. Interestingly, we did not observe significant differences in vaccine reactogenicity between abdominally obese and abdominally non-obese groups. Finally, individuals with a higher body mass index, older age, and previous COVID-19 had higher levels of antibodies induced by COVID-19 and vaccination. Therefore, it is important to evaluate other immunological and inflammatory factors to better understand the pathogenesis of COVID-19 in the presence of risk factors and to propose effective vaccination schedules for vulnerable populations.

[Involvement of matrix metalloproteinases in acute coronary syndrome (ACS)]. / Participación de las metaloproteinasas de matriz en el síndrome isquémico coronario agudo (SICA).

Matrix metalloproteinases (MMP) are enzymes that degrade extracellular matrix (ECM) proteins and regulate both their accumulation and composition. The MMP are involved in the atherosclerotic process since they contribute to the formation of the plaque and its subsequent rupture. This last step triggers the myocardial ischemia that will be clinically reflected as an acute coronary syndrome (ACS). Thus, MMP activity is a key to whether ACS develops or not. With an elevated transcription rate of the genes that codify these proteinases comes a higher enzymatic activity. This explains that if a polymorphism in the mentioned genes modifies transcription, there could be a predisposition to developing ACS. Several studies reveal that certain genetic variations in MMP-1, -2, -3, -7, -8, -9, -12, and -14 have an important role either as risk factors or as protective factors for the expression of ACS.

[Changing the paradigm of congenital heart disease: from the anatomy to the molecular etiology]. / Cambiando el paradigma en las cardiopatías congénitas: de la anatomía a la etiología molecular.

Heart development consists in a group of complex and specific morfogenetic interactions, that requires the proper activity of each factor implicated in this process. Congenital heart defects (CHD) are a group of multifactorial complex diseases with environmental and genetic factors playing important roles. There is not an exact relation between molecular mechanisms and morphological defects in CHD, because in most of the cases the proper development of an anatomical structure implies the adequate function of several pathways that may depend of the action of different genes. This review summarizes the genetic factors implied in the normal heart development and the most common gene mutations associated with CHD.

Association of Obesity with SARS-CoV-2 and Its Relationship with the Humoral Response Prior to Vaccination in the State of Mexico: A Cross-Sectional Study.

Obesity is associated with an increased risk of contracting infections. This study aimed to estimate the risk of COVID-19 infection associated with obesity and to assess its role in the specific antibody response against SARS-CoV-2 in 2021. This study included 980 participants from the State of Mexico who participated in a serological survey where they were tested for SARS-CoV-2 IgG anti-S1/S2 and anti-RBD antibodies and asked for height, weight, and previous infection data via a questionnaire. Of the cohort of 980 participants, 451 (46.02%) were seropositive at the time of recruitment (45.2% symptomatic and 54.8% asymptomatic). The risk of SARS-CoV-2 infection with obesity was 2.18 (95% CI: 1.51-3.16), 2.58 (95% CI: 1.63-4.09), and 1.88 (95% CI: 1.18-2.98) for seropositive, asymptomatic, and symptomatic individuals, respectively, compared to those with normal weight. Anti-S1/S2 and anti-RBD IgG antibodies tended to be higher in overweight and obese participants in the seropositive group and stratified by different obesity classes. Additionally, there was a positive correlation between anti-S1/S2 and anti-RBD IgG antibodies and BMI in both men and women in the seropositive group. Obesity is an independent risk factor for SARS-CoV-2 infection when adjusted for confounding variables; however, the relationship between BMI and anti-S1/S2 and anti-RBD IgG antibody levels differed markedly in the presence or absence of symptoms.

Association of the EPAS1 rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen.

Patent ductus arteriosus (PDA) is frequent in preterm newborns, and its incidence is inversely associated with the degree of prematurity. The first choice of pharmacological treatment is ibuprofen. Several genes, including EPAS1, have been proposed as probable markers associated with a genetic predisposition for the development of PDA in preterm infants. EPAS 1 NG_016000.1:g.84131C>G or rs7557402 has been reported to be probably benign and associated with familial erythrocytosis by the Illumina Clinical Services Laboratory. Other variants of EPAS1 have been previously reported to be benign for familial erythrocytosis because they decrease gene function and are positive for familial erythrocytosis because the overexpression of EPAS1 is a key factor in uncontrolled erythrocyte proliferation. However, this could be inconvenient for ductal closure, since for this process to occur, cell proliferation, migration, and differentiation should take place, and a decrease in EPAS1 gene activity would negatively affect these processes. Single-nucleotide polymorphisms (SNPs) in EPAS1 and TFAP2B genes were searched with high-resolution melting and Sanger sequencing in blood samples of preterm infants with hemodynamically significant PDA treated with ibuprofen at the National Institute of Perinatology. The variant rs7557402, present in the EPAS1 gene eighth intron, was associated with a decreased response to treatment (p = 0.007, OR = 3.53). The SNP rs7557402 was associated with an increased risk of pharmacological treatment failure. A probable mechanism involved could be the decreased activity of the product of the EPAS1 gene.

The antiviral effect of metformin on zika and dengue virus infection.

The Dengue (DENV) and zika (ZIKV) virus infections are currently a public health concern. At present, there is no treatment or a safe and effective vaccine for these viruses. Hence, the development of new strategies as host-directed therapy is required. In this sense, Metformin (MET), an FDA-approved drug used for the treatment of type 2 diabetes, has shown an anti-DENV effect in vitro by activating AMPK and reducing HMGCR activity. In this study, MET treatment was evaluated during in vitro and in vivo ZIKV infection and compared to MET treatment during DENV infection. Our results demonstrated that MET has a broad in vitro antiviral spectrum. MET inhibited ZIKV infection in different cell lines, but it was most effective in inhibiting DENV and yellow fever virus (YFV) infection in Huh-7 cells. However, the drug failed to protect against ZIKV infection when AG129 immunodeficient mice were used as in vivo model. Interestingly, MET increased DENV-infected male mice's survival time, reducing the severe signs of the disease. Together, these findings indicate that, although MET was an effective antiviral agent to inhibit in vitro and in vivo DENV infection, it could only inhibit in vitro ZIKV infection.

Impact of the introduction of chikungunya and zika viruses on the incidence of dengue in endemic zones of Mexico.

BACKGROUND: With the arrival of chikungunya (CHIKV) and zika (ZIKV) viruses in Mexico, there was a decrease in diagnosed dengue virus (DENV) cases. During the first years of cocirculation (2015-2017), the algorithms established by epidemiological surveillance systems and the installed capacity limited us to one diagnostic test per sample, so there was an underestimation of cases until September 2017, when a multiplex algorithm was implemented. Therefore, the objective of this study was determine the impact of the introduction of CHIKV and ZIKV on the incidence of diagnosed DENV in endemic areas of Mexico, when performing the rediagnosis, using the multiplex algorithm, in samples from the first three years of co-circulation of these arboviruses. METHODOLOGY AND PRINCIPAL FINDINGS: For this, 1038 samples received by the Central Laboratory of Epidemiology between 2015 and 2017 were selected for this work. Viruses were identified by multiplex RT-qPCR, and the χ2 test was used to compare categorical variables. With the new multiplex algorithm, we identified 2.4 times the rate of arbovirosis as originally reported, evidencing an underestimation of the incidence of the three viruses. Even so, significantly less dengue was observed than in previous years. The high incidence rates of chikungunya and Zika coincided with periods of dengue decline. The endemic channel showed that the cases caused by DENV rose again after the circulation of CHIKV and ZIKV decreased. In addition, 23 cases of coinfection were identified, with combinations between all viruses. CONCLUSIONS AND SIGNIFICANCE: The results obtained in this study show for the first time the real impact on the detected incidence of dengue after the introduction of CHIKV and ZIKV in Mexico, the degree of underestimation of these arboviruses in the country, as well as the co-infections between these viruses, whose importance clinical and epidemiological are still unknown.

SARS-CoV-2 IgG Antibodies Seroprevalence and Sera Neutralizing Activity in MEXICO: A National Cross-Sectional Study during 2020.

Until recently, the incidence of COVID-19 was primarily estimated using molecular diagnostic methods. However, the number of cases is vastly underreported using these methods. Seroprevalence studies estimate cumulative infection incidences and allow monitoring of transmission dynamics, and the presence of neutralizing antibodies in the population. In February 2020, the Mexican Social Security Institute began conducting anonymous unrelated sampling of residual sera from specimens across the country, excluding patients with fever within the previous two weeks and/or patients with an acute respiratory infection. Sampling was carried out weekly and began 17 days before Mexico's first officially confirmed case. The 24,273 sera obtained were analyzed by chemiluminescent-linked immunosorbent assay (CLIA) IgG S1/S2 and, later, positive cases using this technique were also analyzed to determine the rate of neutralization using the enzyme-linked immunosorbent assay (ELISA). We identified 40 CLIA IgG positive cases before the first official report of SARS-CoV-2 infection in Mexico. The national seroprevalence was 3.5% in February and 33.5% in December. Neutralizing activity among IgG positives patients during overall study period was 86.1%. The extent of the SARS-CoV-2 infection in Mexico is 21 times higher than that reported by molecular techniques. Although the general population is still far from achieving herd immunity, epidemiological indicators should be re-estimated based on serological studies of this type.

[Coinfections by SARS-CoV-2 and other respiratory viruses and their clinical outcome]. / Coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico.

Background: SARS-CoV-2 is a coronavirus described for the first time in China, in December 2019. This virus can cause a disease with a very variable spectrum that ranges from asymptomatic cases to deaths. The most severe cases are normally associated with comorbidities and with the age of the patient. However, there are patients who are not part of these risk groups and develop severe cases. Objetive: To determine the association between coinfections by SARS-CoV-2 and other respiratory viruses and their clincal outcome. Material and methods: RT-qPCR was performed to determine the presence of 16 respiratory viruses in 103 confirmed COVID-19 cases. Demographic and comorbid data were collected, and statistical analyzes were performed to determine associations with severity. Results: Of the 103 analyzed cases, 14 (13.6%) presented a coinfection, of these, 92% did not require hospitalization, even in those cases in which the patient presented advanced age and some comorbidities. Conclusions: These results suggest that coinfection of SARS-CoV-2 and other respiratory viruses is not related to a more severe form of COVID-19 and, in some cases, depending on the virus involved, it could even lead to a better prognosis. These findings lay the foundations for the development of new studies that could determine the biological mechanism of this phenomenon.

Introducción: el SARS-CoV-2 es un coronavirus que fue descrito por primera vez en diciembre de 2019 en Wuhan, China. Este virus causa una enfermedad que varía en un espectro de severidad que va desde casos asintomáticos hasta defunciones. Los casos más severos se asocian normalmente con algunas comorbilidades y con la edad del paciente. Sin embargo, existen pacientes que no son parte de estos grupos de riesgo y aun así desarrollan casos graves. Objetivo: determinar la asociación entre las coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico. Material y métodos: se realizó RT-qPCR para determinar la presencia de 16 virus respiratorios en 103 casos confirmados de COVID-19. Se recolectaron datos demográficos y de comorbilidades, y se realizaron análisis estadísticos para determinar asociaciones con gravedad. Resultados: el 13.6% de los casos (14/103) presentaron alguna coinfección, de estos, el 92% nunca requirió ingreso hospitalario, aun en aquellos casos en los que el paciente presentara comorbilidades y edad avanzada. Conclusiones: estos resultados sugieren que la coinfección no está relacionada con un COVID-19 más grave y que, dependiendo del virus involucrado, incluso podría conducir a un mejor pronóstico. Estos hallazgos sientan las bases para nuevos estudios dirigidos a determinar el mecanismo biológico por el cual ocurre este fenómeno y a proponer las estrategias correspondientes para limitar la progresión a casos severos de COVID-19.

Evolutionary analysis of the Chikungunya virus epidemic in Mexico reveals intra-host mutational hotspots in the E1 protein.

The epidemic potential of Chikungunya virus (CHIKV) was recently made evident by its introduction and rapid expansion in the Caribbean and the Americas. We sought to gain a detailed understanding of the dynamics of the epidemic in Mexico, the country with the highest number of confirmed CHIKV cases in the Americas, and to characterise viral evolution at the population and intra-host level. Analysis of the spatiotemporal distribution of 2,739 diagnosed cases in Mexico from December 2014 to December 2015 showed a rapid nationwide expansion of the epidemic with focalisation in the South West of the country. We sequenced the envelope glycoprotein 1 gene (E1) from 25 patients using the Illumina MiSeq platform and report synonymous and non-synonymous consensus mutations. Bayesian phylogenetic analysis using 249 Asian lineage E1 sequences gave updated estimates of nucleotide substitution rates for E1 and time to most recent common ancestor of major lineages. The analysis indicates phylogenetically-related emergent Latin American clusters in South Western Mexico, Nicaragua and Honduras and transmission of American strains in the Pacific islands. Detailed analysis showed that intra-host changes in E1 mainly occurred in two variable regions (E1:189-220 and E1:349-358) in domains II and III, respectively, in residues involved in inter and intra-envelope spike interactions. At the population level, this study sheds light on the introduction and evolutionary dynamics of CHIKV in the Americas. At the intra-host level, this study identifies mutational hotspots of the E1 protein with implications for understanding the relationship between the CHIKV quasispecies, viral fitness and pathogenesis.

PLA2G2A polymorphisms are associated with metabolic syndrome and type 2 diabetes mellitus. Results from the genetics of atherosclerotic disease Mexican study.

The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156) were genotyped by 5' exonuclease TaqMan assays in a group of 338 patients with T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant 1(codom1), dominant (dom) and additive (add) models adjusted by age, gender, body mass index (BMI), smoking habit, and hypertension, the rs876018T allele was associated with increased risk of MetS [Odds Ratio (OR)=1.66, Pcodom1=0.005; OR=1.67, Pdom=0.003; OR=1.49, Padd=0.005] as compared to controls. On the other hand, under several models adjusted by the same variables, the rs3753827A (OR=1.52, Pcodom1=0.039 and OR=1.49, Pdom=0.039) and rs11573156C alleles (OR=6.46, Pcodom1=0.013; OR=6.70, Pcodom2=0.009; OR=6.65, Pdom=0.009) were associated with increased risk of T2DM when compared with controls. In addition, the rs876018T allele was associated with hypercholesterolemia (Pdom=0.017, Padd=0.009) and risk of subclinical atherosclerosis (SA) (Pdom=0.041) in MetS when compared with controls. Also, this allele was associated with SA in T2DM patients (Pdom=0.007). The TAG haplotype was significantly associated with increased risk of MetS (OR=1.54, P=0.006). Results suggest that PLA2G2A polymorphisms are involved in the risk of developing MetS and T2D and are associated with SA in this group of patients.

Prevalence of non-influenza respiratory viruses in acute respiratory infection cases in Mexico.

BACKGROUND: Acute respiratory infections are the leading cause of morbidity and mortality worldwide. Although a viral aetiological agent is estimated to be involved in up to 80% of cases, the majority of these agents have never been specifically identified. Since 2009, diagnostic and surveillance efforts for influenza virus have been applied worldwide. However, insufficient epidemiological information is available for the many other respiratory viruses that can cause Acute respiratory infections. METHODS: This study evaluated the presence of 14 non-influenza respiratory viruses in 872 pharyngeal exudate samples using RT-qPCR. All samples met the operational definition of a probable case of an influenza-like illness or severe acute respiratory infection and had a previous negative result for influenza by RT-qPCR. RESULTS: The presence of at least one non-influenza virus was observed in 312 samples (35.8%). The most frequent viruses were rhinovirus (RV; 33.0%), human respiratory syncytial virus (HRSV; 30.8%) and human metapneumovirus (HMPV; 10.6%). A total of 56 cases of co-infection (17.9%) caused by 2, 3, or 4 viruses were identified. Approximately 62.5% of all positive cases were in children under 9 years of age. CONCLUSION: In this study, we identified 13 non-influenza respiratory viruses that could occur in any season of the year. This study provides evidence for the prevalence and seasonality of a wide range of respiratory viruses that circulate in Mexico and constitute a risk for the population. Additionally, our data suggest that including these tests more widely in the diagnostic algorithm for influenza may reduce the use of unnecessary antibiotics, reduce the hospitalisation time, and enrich national epidemiological data with respect to the infections caused by these viruses.

Coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico / Coinfections by SARS-CoV-2 and other respiratory viruses and their clinical outcome

Introducción: el SARS-CoV-2 es un coronavirus que fue descrito por primera vez en diciembre de 2019 en Wuhan, China. Este virus causa una enfermedad que varía en un espectro de severidad que va desde casos asintomáticos hasta defunciones. Los casos más severos se asocian normalmente con algunas comorbilidades y con la edad del paciente. Sin embargo, existen pacientes que no son parte de estos grupos de riesgo y aun así desarrollan casos graves. Objetivo: determinar la asociación entre las coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico. Material y métodos: se realizó RT-qPCR para determinar la presencia de 16 virus respiratorios en 103 casos confirmados de COVID-19. Se recolectaron datos demográficos y de comorbilidades, y se realizaron análisis estadísticos para determinar asociaciones con gravedad. Resultados: el 13.6% de los casos (14/103) presentaron alguna coinfección, de estos, el 92% nunca requirió ingreso hospitalario, aun en aquellos casos en los que el paciente presentara comorbilidades y edad avanzada. Conclusiones: estos resultados sugieren que la coinfección no está relacionada con un COVID-19 más grave y que, dependiendo del virus involucrado, incluso podría conducir a un mejor pronóstico. Estos hallazgos sientan las bases para nuevos estudios dirigidos a determinar el mecanismo biológico por el cual ocurre este fenómeno y a proponer las estrategias correspondientes para limitar la progresión a casos severos de COVID-19.

Background: SARS-CoV-2 is a coronavirus described for the first time in China, in December 2019. This virus can cause a disease with a very variable spectrum that ranges from asymptomatic cases to deaths. The most severe cases are normally associated with comorbidities and with the age of the patient. However, there are patients who are not part of these risk groups and develop severe cases. Objetive: To determine the association between coinfections by SARS-CoV-2 and other respiratory viruses and their clincal outcome. Material and methods: RT-qPCR was performed to determine the presence of 16 respiratory viruses in 103 confirmed COVID-19 cases. Demographic and comorbid data were collected, and statistical analyzes were performed to determine associations with severity. Results: Of the 103 analyzed cases, 14 (13.6%) presented a coinfection, of these, 92% did not require hospitalization, even in those cases in which the patient presented advanced age and some comorbidities. Conclusions: These results suggest that coinfection of SARS-CoV-2 and other respiratory viruses is not related to a more severe form of COVID-19 and, in some cases, depending on the virus involved, it could even lead to a better prognosis. These findings lay the foundations for the development of new studies that could determine the biological mechanism of this phenomenon.

In Silico Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential.

The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.

Novel mutations in the transcriptional activator domain of the human TBX20 in patients with atrial septal defect.

BACKGROUND: The relevance of TBX20 gene in heart development has been demonstrated in many animal models, but there are few works that try to elucidate the effect of TBX20 mutations in human congenital heart diseases. In these studies, all missense mutations associated with atrial septal defect (ASD) were found in the DNA-binding T-box domain, none in the transcriptional activator domain. METHODS: We search for TBX20 mutations in a group of patients with ASD or ventricular septal defect (VSD) using the High Resolution Melting (HRM) method and DNA sequencing. RESULTS: We report three missense mutations (Y309D, T370O, and M395R) within the transcriptional activator domain of human TBX20 that were associated with ASD. CONCLUSIONS: This is the first association of TBX20 transcriptional activator domain missense mutations with ASD. These findings could have implications for diagnosis, genetic screening, and patient follow-up.