ABSTRACT
Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36-3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p.Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future.
Subject(s)
Cytoskeletal Proteins/genetics , Heart Septal Defects, Atrial/genetics , Mutation , Myosin Heavy Chains/genetics , Myosin Type III/genetics , Adolescent , Adult , Amino Acid Sequence , Amino Acid Substitution , Base Sequence , Case-Control Studies , Child , Child, Preschool , Conserved Sequence , Cytoskeletal Proteins/chemistry , Female , Humans , Male , Middle Aged , Models, Genetic , Models, Molecular , Mutation, Missense , Myosin Heavy Chains/chemistry , Myosin Type III/chemistry , Polymorphism, Single Nucleotide , Young AdultABSTRACT
Ventricular septal defect (VSD) is the most common form of cardiac malformations accounting approximately 20% of all congenital heart defects. SMAD7 is an inhibitory protein that antagonizes the signalling of TGF-ß family member and has been found in the development and function of mouse heart models. This study aims to screen and identify the polymorphisms of SMAD7 exonic regions in Malay population with VSD. Peripheral blood samples were collected and extracted from 30 clinically diagnosed VSD patients. PCR amplification was performed using 12 sets of designed primers encompassing seven exons of SMAD7. Re-sequencing was conducted to characterize the polymorphisms of SMAD7. Observed polymorphisms were then genotyped in 30 healthy individuals using both re-sequencing and allele-specific PCR techniques. A total of 10 variants were identified in the patient population located in the upstream (rs7236774), exonic (rs368427729, rs145686330, rs3764482, rs3809922, rs780863704 and rs3809923), intronic (rs3736242) and 3'UTR regions (rs375444823 and rs16950113). No significant difference of genotype and allele frequency was observed among these SNPs. Two synonymous variants (rs3809922 and rs3809923) were found in complete linkage disequilibrium (r2=1.0) with each other indicate a strong correlation of these SNPs. The identification of these SNPs provides a new perspective of the VSD causation.
ABSTRACT
<p><b>INTRODUCTION</b>This study aimed to determine the prevalence of asthma-like symptoms among schoolchildren with low birth weight (LBW), and to compare the lung function of these children with that of children with normal birth weight.</p><p><b>METHODS</b>This was a comparative cross-sectional study. We recruited children aged 8-11 years from eight primary schools in Kota Bharu, Kelantan, Malaysia. The children were divided into two groups: those with LBW (< 2,500 g) and those with normal birth weight (≥ 2,500 g). Parents of the enrolled children were asked to complete a translated version of the International Study of Asthma and Allergies in Childhood questionnaire. Lung function tests, done using a MicroLoop Spirometer, were performed for the children in both groups by a single investigator who was blinded to the children's birth weight.</p><p><b>RESULTS</b>The prevalence of 'ever wheezed' among the children with LBW was 12.9%. This value was significantly higher than that of the children with normal birth weight (7.8%). Forced vital capacity (FVC), forced expiratory volume in one second, and forced expiratory flow when 50% and 75% of the FVC had been exhaled were significantly lower among the children with LBW as compared to the children with normal birth weight.</p><p><b>CONCLUSION</b>LBW is associated with an increased prevalence of asthma-like symptoms and impaired lung function indices later in life. Children born with LBW may need additional follow-up so that future respiratory problems can be detected early.</p>
