Background: The chromosomal polymorphism of short arms of acrocentric chromosomes and heterochromatin variation of Chromosomes 1, 9, 16 and Y have been reported in humans. The pericentric inversion of Chromosome 9 is commonly seen in normal humans and the frequency estimated to be 1 to 3% in general population and inherited in mendalian fashion or might occur spontaneously without any clinical significance. Aim: The aim of the study was to study the frequency of inv(9) and its clinical correlation with human genetic diseases. Materials and Methods:0 The chromosomal analysis using GTG-banding was carried out in 3,392 cases suspected with genetic diseases. Results: The pericentric inversion frequency of different chromosomes in our study was 1.24% and frequency of inv(9)(p12q13) was high (64.29%) compared to other pericentric inversions in our study. A high frequency (9.33%) of inv(9)(p12q13) was detected in children with dysmorphic features and congenital anomalies. Conclusion: As a high frequency of inv(9)(p12q13) detected in children with dysmorphic features, the inv(9) definitely have a role in the abnormal phenotype development. During inversion event there might be loss or suppression of euchromatin chromosome region and hence detailed chromosomal break point study is important to understand the clinical significance of the pericentric inversion of Chromosome 9.

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She was brought to our Institute at the age of 31, with speech delay and mental handicap. She was assessed by the multidisciplinary team in the institute to determine the cause of her problems. Clinical evaluation revealed dysmorphic facial features, microbrachycephaly, camptodactyly, clinodactyly, abnormal dermatoglyphics and severe mental handicap. Cardiovascular system examination was normal. Chromosomal analysis revealed a trisomy of Chromosome 18. The phenotype of trisomy 18 and the rarity of prolonged survival in this case are discussed.

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Background : Rubella is a contagious viral infection associated with rash. 10-15% of women are susceptible to this infection in their childbearing years and the disease is usually transmitted to the developing fetus causing abortion or stillbirth or congenital Rubella syndrome (CRS). Sensorineural hearing loss is one of the most common abnormalities associated with CRS. Aims : The study was undertaken to determine the prevalence of Rubella induced congenital deafness in south India. Materials and Methods :The present study is carried out on 1076 hearing impaired children below 14 years of age to determine etiological factors for congenital hearing impairment. Various audiometric tests such as PTA, OAE and BERA were carried out to know the type and degree of hearing impairment. Development histories including the prenatal, perinatal and postnatal histories were collected using a standard questionnaire. Results :The results indicated very less percentage (1.57%) of cases with the history of maternal Rubella infection indicating a significant reduction of Rubella-induced deafness in the developing countries. Conclusions : The main reason behind the low percentage of children with rubella- induced hearing impairment may be due to appropriate immunization of mothers to the rubella infection during their child bearing years. The increasing awareness in the developing countries of this infection and its consequences is another important reason behind the low percentage of the affected population.

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A four-day-old neonate presented with severe abdominal distention, intermittent bilious vomiting, typical black lock, partial albinism and heterochromatic iris. Ileostomy was done proximal to the transition zone at mid-ileal region (50 cms proximal to ileo-cecal region) All biopsy specimens till the transitional zone were negative for ganglion cells. Distinct features of total colonic aganglionosis and recto-sigmoid Hirschsprung's disease are delineated here.

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Background: An abnormal karyotype in either partner, especially featuring a translocation and/or inversion is considered to be a cause of recurrent miscarriages. It is generally assumed that recurrent miscarriage might be due to recurrent chromosomal abnormalities in the fetus due to a balanced aberration in one of the parents being inherited by the offspring in an unbalanced form. Aim: Evaluation of chromosomal rearrangements in couples with recurrent miscarriages. Materials and Methods: Peripheral blood was collected and lymphocyte cultures were set up. Slides prepared from the cell suspension were stained and screened for metaphases followed by karyotyping. Result: Balanced translocation was observed in the male partner in one case and in the female partners in the three other cases. Conclusion: Couples with recurrent miscarriage should be investigated for chromosomal rearrangements, thus helping in genetic counseling and providing the options for future pregnancies.

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Background : Pulmonary tuberculosis is caused by Mycobacterium tuberculosis . It is a multifactorial disease with both host as well as pathogen factors contributing to susceptibility and protection from the disease. Various reports have highlighted important roles of lung surfactant protein D (SP-D), mannan-binding lectin (MBL) and I-NOS in innate immune defense against M. tuberculosis Aims : The present study investigated the role of polymorphisms in three candidate genes encoding Lung surfactant protein D, Mannan binding lectin and Inducible Nitric oxide synthase, in susceptibility and protection to pulmonary tuberculosis. Settings and Design : A case-control association study of SNP's in lung surfactant protein D (SP-D), mannan-binding lectin (MBL) and I-NOS with pulmonary tuberculosis in Indian population was carried out. This involved sequencing of all the coding exons of lung surfactant protein D (SP-D) , while, exon 1 (collagen region) and exon 4 (carbohydrate recognition domain) of mannan-binding lectin (MBL) and exons 2, 8 and 16 of I-NOS and their flanking intronic regions for single nucleotide polymorphisms in DNA samples isolated from 30 pulmonary tuberculosis patients and 30 controls of Indian population. Statistical analysis: Various allele frequencies were calculated using online two by two table (home.clara.net/sisa/). Odds ratio and P values were calculated at 95% confidence interval (CI). Results : A total of fourteen single nucleotide polymorphisms (5 in SP-D , 5 in MBL and 4 in I-NOS ) were observed of which four (G459A SP-D , G274T I-NOS , G1011A and T357G MBL ) have not been reported earlier. Four single nucleotide polymorphisms viz. G459A of exon 7 of SP-D ( P =0.00, odds ratio (OR) = 4.96, 2.18 P = 0.00 or= 3.85 1.66 P =0.00 or=4.04, 2.20< OR<7.42) and G274T of intron 16 of I-NOS ( P =0.00 or=4.46, 2.40 Conclusion: The present study has led to identification of 4 SNP's in SP-D , MBL and I-NOS associated with pulmonary tuberculosis in Indian population.

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Background : Endoglin , is a component of transforming growth factor-β complex. It is involved in vascular development and structural maintenance of the vessel wall. Conflicting reports on the association of a six base insertion polymorphism in intron 7 of the endoglin gene in intracranial aneurysms (IA) have been reported earlier. materials and Methods: A case-control study was designed to compare 102 South Indian patients with intracranial saccular aneurysms and 118 ethnically and geographically matched healthy controls. The frequency of the six base insertion polymorphism was assessed by heteroduplex analysis followed by direct sequencing. Results:Insertion allele count was 39 (19.1%) of 204 alleles in the patient group and 42 (17.8%) of 236 alleles in the control group. The INS allele frequency was similar to the frequency in Caucasian population, but it was significantly lower than the Japanese population ( P =0.01). There was also no relationship of this polymorphism in patients with single aneurysm (33/176 alleles) or those with multiple aneurysms (6/28 alleles). Conclusion:Six base insertion polymorphism in Endoglin gene was not found to be a risk factor for intracranial saccular aneurysms in the South Indian population. Ethnic-related differences were observed. This is the first report on any genetic mutation in intracranial aneurysms in Indian population.

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Background: Duodenal ulcer (DU) is a multifactorial disorder with different etiological and pathogenetic mechanisms. Evidence for the role of genetic factors such as familial aggregation, twin studies, ABO blood groups, ABH nonsecretor status and hyperpepsinogenemia have been reported in DU. Genetic heterogeneity of cases with familial incidence will provide information regarding the association of qualitative and quantitative traits. Aim: Hence, the present study is envisaged at identifying the segregant and deviant groups based on parental phenotypes and their association with other quantitative markers. Materials AND Methods: 62 out of 462 endoscopically confirmed duodenal ulcer cases were considered for the analysis of genetic heterogeneity. This was resolved through the calculation of genetic risk estimates of sporadic cases in multiplex families based on different modes of inheritance and variation in associated genetic and biochemical markers. Results: Mean age at onset in simplex and multiplex cases was found to vary indicating the presence of genetic heterogeneity in the expression of the disease. Segregant and deviant groups were identified based on mortons probability risk estimates and examined for the possible association of qualitative and quantitative markers such as pepsinogen phenotype, serum and tissue pepsinogen levels, cathepsin E, malondialdehyde and ceruloplasmin levels. Conclusions: The study thus highlighted the presence of genetic heterogeneity in the expression of the disease. The risk factors associated with segregant type were normal serum and tissue pepsinogen levels increased malondialdehyde levels and association of AC phenotype while the deviant group was characterized by early age at onset with hyper pepsinogenemia and reduced cathepin E levels.

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Background:During the last five years the proportion of living unrelated kidney transplants has increased and DNA tissue-typing methods have become popular in India. This study was carried out to compare the results of tissue - typing by serology and sequence specific primers (SSP) and study the usefulness of 'episode' allograft biopsies for diagnosis of acute graft dysfunction . Materials and Methods:DNA was extracted from whole blood using Qiagen kit. Samples from 60 individuals including thirty patients and their donors were typed by serology and SSP. Fifteen allograft biopsies were performed for suspected acute rejection (AR) cases. Results: Both alleles of HLA - A, B and DR antigen could be determined in 86, 65 and 90% of samples by SSP respectively. There was a discrepancy of 16-40% between SSP and serology. Acute rejection was confirmed in 8/15 biopsies. Graft survival rates were 83 and 76% at one and two years respectively. Neither the graft survival nor the number of AR episodes showed any correlation with the extent of HLA mismatch. SSP was useful in defining A*68, A*66, A*69 and A*33 alleles at private level and A*36, A*74 and A*03 alleles which were blank on serology. Conclusions: SSP has become popular in India due to its simplicity, superior results especially for class II HLA alleles: and episode allograft biopsy is adequate for follow-up of kidney recipients.

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Background:Cu-Zn superoxide dismutases are antioxidative defensive enzymes that catalyze the reduction of superoxide anions to hydrogen peroxide. Aim:The study focuses on the association of electromorph of superoxide dismutase with duodenal ulcers, which result due to an imbalance between aggressive and defensive factors. Materials and Methods:Endoscopically confirmed 210 duodenal ulcer patients and 185 healthy individuals for comparative analysis were considered for the present study. Phenotyping of superoxide dismutase was carried out by subjecting the RBC membranes to polyacrylamide gel electrophoresis, using appropriate staining protocols. Results:Statistical analysis of SOD phenotypes revealed a significant increase of SOD A*2 allele and Superoxide dismutases (SOD) 2-2 phenotype in duodenal ulcer group. Among these individuals, a predominance of Helicobacter pylori infection was observed. The increased preponderance of homozygotes can be explained on the basis of reduced and altered enzyme activity, which may lead to disturbance in homeostasis of antioxidant/oxidant culminating in high lipid peroxidative gastric mucosal tissue damage and ulceration. No variation in the distribution of SOD phenotypes with respect to Helicobacter pylori indicates the role of Mn-SOD rather than Cu-Zn SOD in the Helicobacter pylori infected cases as reported earlier. Conclusions:Superoxide dismutase as a genetic marker / gene modifier, encoding for an antioxidant enzyme in maintaining tissue homeostasis of the gastric mucosa is discussed.

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