Balasundaram Krishnamurthy

Prevalence of congenital heart diseases in Mysore

Background: Prevalence studies on Congenital heart Diseases (CHDs) have been done several times world wide and such studies are very limited in Indian populations. A few earlier studies in India have reported an increased prevalence of CHDs ranging from 2.25 to 50.89 per 1000 live births. Aims and Objective: To study the prevalence of congenital heart diseases in Indian population. Materials and Methods: Data on the prevalence of CHDs were collected and analyzed from the three major hospitals of Mysore, Cheluvamba Hospital, CSI Holdsworth Memorial Hospital and J.S.S Hospital from the year 2000 to 2004. Results: The prevalence of CHDs for five years in Mysore hospitals ranges from 6.6 to 13.06 per 1000 live births. The most frequent type of CHD was found to be VSD (40.47%) followed by ASD (19.06%), TOF (13.38%) and PDA (9.53%). It is clear that the maximum CHDs were detected in the first year of life when compared to the later years of life. The prevalence of CHDs in Mysore is increasing from 2000 to 2004 which might be due to the improvement of diagnosis, attention or awareness among the medical authorities on the disease. Conclusion: The prevalence of CHDs in Mysore is not very high as reported in other parts of the country, however; it is an important disease which needs an immediate medical attention.

De novo isochromosome 18p in a female dysmorphic child

Isochromosome 18p results in tetrasomy 18p. Most of the i(18p) cases reported so far in the literature are sporadic due tode novo formation, while familial and mosaic cases are infrequent. It is a rare chromosomal abnormality, occurring once in every 140 000 livebirths, affecting males and females equally. In the present investigation, we report ade novo i(18p) in a female dysmorphic child. The small metacentric marker chromosome was confirmed as i(18p) in the proband by cytogenetic and FISH analysis [47,XX + i(18p)]. Cytogenetic investigations in the family members revealed normal chromosome numbers, indicating the case as ade novo event of i(1 8p) formation. It could be due to the somewhat advanced maternal age (32 years) and/or expression of recessive genes in the proband, who is the progeny of consanguineous marriage, which could have led to misdivision and nondisjunction of chromosome 18 in meiosis I, followed by failure in the chromatid separation of 18p in meiosis II and by inverted duplication.

A Maiden Report on CRELD1 Single-Nucleotide Polymorphism Association in Congenital Heart Disease Patients of Mysore, South India

Cardiac malformations contribute greatly to cardiovascular disease in the young, constituting a major portion of clinically significant birth defects. Congenital heart disease (CHD) is a common congenital cardiac birth defect, affecting nearly 1% of all live births. Although significant advances have been made in understanding mechanisms controlling heart formation, the causes of most CHD in humans remain undefined in the vast majority of cases. Of the several genes identified for CHD, CRELD1 is an important cell adhesion molecule crucial in cardiac development, which is known to cause atrioventricular septal defect in Down syndrome and also in sporadic forms of atrioventricular septal defect. With informed consent, 100 clinically diagnosed CHD patients and 50 healthy controls in Mysore, South India, were recruited for single-nucleotide polymorphism (SNP) genotyping. MassARRAY analysis of five prominent SNPs of CRELD1 was performed. The analysis revealed the occurrence of the SNP c.985 C>T of CRELD1 in two of CHD patients and not in controls. This SNP shows a change from arginine to cysteine in the second calcium-binding epidermal growth factor (EGF) domain, leading to change in the β-sheet in the secondary structure. Therefore, the SNP c.985 C>T of CRELD1 is involved in causing CHD in patients of Mysore, South India.

Missense mutation G296S in GATA4 is not responsible for cardiac septal defects.

BACKGROUND: The most common type of congenital heart disease is the cardiac septal defects, which has reported to be caused by a missense mutation (G296S) in exon 3 of the GATA4 gene. AIMS: The present study was undertaken to find out whether GATA4 gene is the prime cause of the septal defects in Mysore population. MATERIALS AND METHODS: GATA4 gene analyses were undertaken on 21 confirmed CHD cases by PCR and DNA sequencing. RESULTS AND CONCLUSION: Analysis of this particular mutation in 21 septal defect patients revealed that none of the patients had the mutation, indicating that this mutation is population specific or septal defect in Mysore population is caused due to mutations in other regions of the GATA4 gene.

GATA4 Specific Nonsynonymous Single-Nucleotide Polymorphisms in Congenital Heart Disease Patients of Mysore, India

Congenital heart disease (CHD) is the most common type of birth defect, affecting 1% of all live births. The recent exponential increase in the knowledge of medical genetics has revolutionized the understanding of CHDs during the past few decades. GATA4, a transcription factor, is involved in heart development. There are many contradictory reports on involvement of single-nucleotide polymorphisms (SNPs) of GATA4 in the manifestation of CHD. In view of this, an attempt has been made to analyze the known SNPs of GATA4 in Mysore patients with CHD. Of the 308 CHD patients recruited, 100 were screened for SNPs of GATA4 by MassARRAY, which identified 11 SNPs, of which 6 were found in both CHD cases and controls. The other 5 SNPs, c.278G>C (G93A), c.1207C>A (L403M), c.1232C>T (A411V), c.1295T>C (L432S), and c.1180C>G (P394A), were found only in CHD patients. Secondary structure analysis revealed that mutant proteins with the SNPs G93A, L403M, and L432S showed structural changes in their helix, sheet, and turn. Thus, these findings suggest the involvement of specific SNPs of GATA4 in the manifestation of CHD, reported for the first time in an Indian scenario. However, screening for a larger number of CHD patients would help us to establish genotype-phenotype correlation.

Chromosomal Anomalies and Congenital Heart Disease in Mysore, South India

Abstract Congenital heart disease (CHD) is the most common form of human birth defects accounting for about 30% of the total anomalies. The prevalence of CHD worldwide is found to range between 1.0 – 150/ 1000 live births. The causes for CHD can be categorized into three major groups such as, chromosomal (0.4 - 26.8%), single gene disorders (10-15%) and multiple factors (85-90%). Here we report the association of chromosomal variations with CHD in Mysore. A total of 192 confirmed CHD cases were considered for the present study whose age ranged from 1 day to 23 years. After written consent was obtained from the family members, 136 CHD patients were subjected for conventional cytogenetic studies and some of them for FISH analysis. Of these, 18 patients were with numerical abnormalities, 3 patients with structural abnormalities, one patient with both numerical and structural abnormalities and remaining 114 patients with normal chromosomes. Thus, the present findings are the maiden report from Mysore, which have contributed richly towards the association of chromosomal anomalies with CHD and pointing out chromosome 9 a possible killer chromosome for the cause of CHD.

Mutations of TFAP2B in congenital heart disease patients in Mysore, South India.

Background & objectives: Cardiac malformations in the young constitute a major portion of clinically significant birth defects. Congenital heart disease (CHD) is a common congenital cardiac birth defect, affecting nearly 1 per cent of all live births. Patent ductus arteriosus (PDA) is clinically significant foetal circulation anomaly, second most common form of CHD which constitutes approximately 10 per cent of total CHDs. The study aimed to screen for TFAP2B mutations in CHD patients of Mysore. Methods: With informed consent, 100 clinically diagnosed CHD patients and 50 healthy controls in Mysore, south India, were recruited for the analysis of screening of mutations. MassARRAY analysis of 5 prominent mutations of TFAP2B was performed. Results: The analysis did not show any of the five mutations of TFAP2B screened by massARRAY in patients and controls, indicating that these mutations were not involved in the manifestation of CHD in the patients at Mysore, south India. Interpretation & Conclusions: The findings suggest the lack of involvement of known mutations of TFAP2B with syndromic or nonsyndromic CHDs in Mysore patients.

A rare case of congenital heart disease with ambiguous genitalia

Birth defects have become the important cause of mortality and morbidity in the perinatal period. Congenital heart disease (CHD) is the most common birth defect which includes the varying forms of cardiac abnormalities and occurs with an incidence of 1 per 100 live births. In most of the cases, CHD is an isolated malformation, but about 33% have associated anomalies. Ambiguous genitalia are one such rare anomaly that is associated with CHD among other genital abnormalities. The possible causes for this association could be pseudohermaphroditism, which in turn, may be due to congenital adrenal hyperplasia. The government of any country should consider providing for its people a free prenatal diagnosis for susceptible disorders.

Association between pericentric inversion in chromosome 9 and congenital heart defects

Abstract Congenital heart disease (CHD) is the leading cause of mortality in the first year of life. Prevalence of CHD worldwide is found to range from 1.0 to 50.89 per 1000 livebirths including India. The association of these defects with chromosomal anomalies varies between 4 to 12%. In the present investigation, we report two different cases of pericentric inversion of chromosome 9 [inv(9)(p11-q13)], associated with Total Anomalous Pulmonary Venous Connection (TAPVC) and Tetralogy of Fallot (TOF). In one of the cases (TOF), the mother had similar inversion without CHD. We predict here that, the genes responsible for the normal heart development could be present on chromosome 9 around p11-q13 region, which might have been defective during the process of inversion and thereby resulted in CHD. To our knowledge, this is the maiden report of association of inversion with CHD from South India.

Rare association of turner syndrome with neurofibromatosis type 1 and tuberous sclerosis complex

We report a rare association of Turner syndrome with both Neurofibromatosis type I and Tuberous Sclerosis. The patient had XOkaryotype with Turners stigmata and also had features of Neurofibromatosis 1 in the form of significant café-au-lait spots and Plexiform neurofibroma along with typical features of Tuberous Sclerosis complex. Pedigree analysis revealed that the elder brother of the proband in the family also suffered from Tuberous Sclerosis without the manifestation of Neurofibromatosis or any other genetic disorders. We hypothesize that these associations could be due to new independent mutations and also increased maternal and paternal age in a pre-disposition of Turner syndrome.