Maternal grandmothers with advanced age reproduction are more likely to have Down syndrome grandchildren

Down syndrome (DS), trisomy 21, is the most common chromosomal syndrome that affects one in 600-800 live births. The advanced maternal age is the only well known risk factor to cause DS. Our study revealed that many young mothers produced DS children than advanced age mothers in India. A total of 150 suspected DS cases were investigated cytogenetically. Randomly selected 200 healthy families in South India were used as controls. Logistic regression was performed on case-control dataset which was generated by randomly selecting the child from each of the control families. Pedigree analyses indicated that the maternal grandmothers had advanced age during conception of their daughters who gave birth to DS child. Case-control status was used as dependent variable, whereas parental and grandparental age was used as covariates. Logistic regression was reported as odds ratios, univariate and multivariate. The age of maternal grandmother showed highly significant difference in odds ratio, indicating that the advanced age of maternal grandmother was the possible risk factor.  Therefore, it is important to sort-out the effect of advanced age mothers vs grandmothers on increased frequency of DS reported in different populations

Inheritance patterns, consanguinity & risk for asthma

Background & Objectives: Family history is an important risk factor for the development of asthma, contingent upon genetic and environment interaction. Since there is paucity of data on asthma inheritance in Indian population, the present study was undertaken to investigate the inheritance patterns of asthma and the effect of family history and consanguineous marriage on asthma inheritance. Methods: A total of 200 families, 100 index children and 100 index adults with clinically diagnosed asthma, along with 400 non-asthmatic children and adults as controls were selected for the present study. Information about the family history of each patients and controls was collected and analyzed pedigrees were also constructed. Results: A history of asthma in any member of the family was observed in 44.5 per cent of cases and 5.3 per cent of controls (P<0.001). A differential risk of developing asthma was noted in family history of asthma in different first and second degree relatives of children and adult patients. Consanguineous marriage was also noted in parents in 24.5 per cent of cases and 12.3 per cent of controls (P<0.001). The most common mode of asthma inheritance was recessive. Interpretation & Conclusions: Our results showed that consanguineous marriage and family history of asthma are important determinants in the development of asthma in the offspring

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 XO karyotype with Turners stigmata and also had features of Neurofibromatosis 1 in the form of significant cafe-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

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 XO karyotype with Turners stigmata and also had features of Neurofibromatosis 1 in the form of significant cafe-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

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

Short Communication - 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

Short Communication - 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

Nuclear Co-repressor 1: A Potential Candidate Gene in the Manifestation of Congenital Heart Diseases

The heart is the first organ formed during embryogenesis. The development of the heart is controlled by a network of pathways involving various transcription factors and signalling. Disruptions of these factors lead to the manifestation of congenital heart disease (CHD). The ventricular septal defects (VSD) of CHD are more frequent in the Indian population, particularly in Mysuru. In view of this, to identify defective genes in ventricular septal development, whole-exome sequencing was performed in seven cases of non-syndromic VSDs and three cases of Tetralogy of Fallot. The exome data analysis revealed that of all the defective genes identified, Nuclear Co-repressor 1 (NCoR1) is the prominent gene. It showed four non-synonymous damaging single nucleotide variants, that is, G244A, C241T, G207C and G121A. These mutations were present in the GPS2 protein domain, an integral part of NCoR1-HDAC complex involved in myogenesis. Further, pathway enrichment and network analysis indicated that NCoR1 interacts with HEY1, HEY2, MEF2A, NOTCH2 and HDAC3 proteins involved in heart development. Hence, defects in NCoR1 are responsible for VSD in heart development

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