Anupam Kaur

Recurrent pregnancy loss: TNF-α and IL-10 polymorphisms.

BACKGROUND: The recurrent pregnancy loss requires careful consideration of genetic, anatomic, endocrine, infectious and immunological factors. Cytokine gene polymorphisms in the promoter regions of tumor necrosis factor (TNF)-α and interleukin (IL)-10 are associated with recurrent pregnancy loss. AIM: The aim of present study was to investigate the association of the IL-10 -592C/A and TNF-α-308 G/A, promoter polymorphisms among women with at least three consecutive miscarriages. MATERIALS AND METHODS: Genotyping was done in 50 women with RPL for IL-10-592C/A and TNF-α-308G/A promoter polymorphism to see the association of these loci with pregnancy loss. The control group included 50 healthy women having two or more children (mean age of the female subjects 35 years) for statistical comparisons. RESULTS: IL- 10-592C/A and TNF-α-308G/A promoter polymorphisms were not associated with the recurrent miscarriages. CONCLUSIONS: There is a need to screen a larger sample and in different ethnic groups using IL-10-592C/A and TNF-α-308G/A markers to understand their association with recurrent miscarriages. This would further help in efficient management of immunologically mediated recurrent miscarriages at the sample/individual level.

Cytogenetic Analysis in Cases with Sex Anomalies

Abstract The relationship between abnormal chromosomal constitution and sex anomalies has been established since the development of cytogenetic methods. Determination of chromosomal status is the prerequisite for precise diagnosis and counseling of any case with sex anomaly. It is also essential for defining genotypic and phenotypic correlation and understanding the basic mechanism involved in sex determination. In the present study, 156 cases with sex anomalies were investigated. 40 cases (25.6%) showed abnormal karyotypes. These included 10 cases with mosacism, of which 7 were with 45,X/46,XX chromosomal complement; 2 had marker chromosome, 45,X/46,X,+mar; and 1 case showed 46,XY/47,XXY constitution.

Chromosomal Abnormalities: Genetic Disease Burden in India

Abstract Chromosomal abnormalities are frequent events. Globally, at least 7.6 million children are born annually with severe genetic or congenital malformations. Precise prevalence data are difficult to collect, especially in India, owing to great diversity of conditions and also because many cases remain undiagnosed. Genetic and congenital abnormality is the second most common cause of infant and childhood mortality and occurs with a prevalence of 25-60 per 1000 births. The higher prevalence of genetic diseases in a particular community may, however, be due to some social or cultural factors.

CYTOGENETIC PROFILE OF INDIVIDUALS WITH MENTAL RETARDATION

Abstract The incomplete development of mental capacities and associated behavioural abnormalities are referred to as mental retardation. It is single largest neuropsychiatric disorder in every civilised society affecting 2.5-3.0% of the total population. Chromosomal abnormalities are the important cause of mental retardation. Cytogenetic investigations were carried out on 143 mentally subnormal individuals that were referred to the Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, India, during 1996 to 2002. These cases were referred mainly as suspected Down syndrome, delayed milestones, mental retardation, etc. The age group of the patients ranged from 1 month to 18 years. Interestingly, maximum number of patients i.e., 58/143 (40.5%) were the firstborns and the average maternal age was 27.6 years. Free trisomy 21 was found to be the most frequent autosomal aberration, both amongst males and females (45.4% males, 18.8% females). It was seen in 92/143 (64.3%) cases while translocations were seen in 2.7% cases. The latter included 45,XY,+t(13;14), 46,XY,+t(14;21), 45,XX,+t (14;21) and 46,XX,+t(14;21) karyotypes.

Ring chromosome 7 in an Indian woman

Abstract Background Ring chromosome 7 [r(7)] is a rare cytogenetic aberration, with only 16 cases (including 3 females) reported in the literature to date. This is the first reported case of r(7) from India. Method Clinical and cytogenetic investigations were carried out in an adult female with microcephaly and intellectual disability. Results Ring chromosome 7 was observed in 10% of the metaphases (46,XX,r(7)/46,XX). The clinical findings revealed microcephaly, growth delay, and dark pigmented naevi. Conclusion The mosaicism for a chromosomal anomaly is an under‐recognised cause of intellectual disability.

The Micronucleus Test in Urothelial Cells and Uterine Smears of Cervix Cancer Patients: A Comparison

Abstract Cytogenetic damage was assessed using the (MN) test in urothelial cells and cervix smears of local cervix cancer patients since the genetic end-point screening for micronuclei provides a measure of both, chromosome breakage and loss. The MN data were grouped for stage-types of cancer, age-groups, age-atmarriage, parity levels and socio-economic status. A comparison of the results obtained from both the tissues has revealed that the percent frequency of MNd cells was elevated in urothelial cells except when the variable for age-groups of the patients was compared. If validated, the MN assay in urothelial cells may prove useful for screening programmes for cervix cancer as besides scoring effectively for cytogenetic damage, it utilizes a non-invasive process of sample collection.

Prevalence of methylenetetrahydrofolate reductase 677 C‑T polymorphism among mothers of Down syndrome children

INTRODUCTION: The relationship between chromosomal non-disjunction leading to aneuploidy and folate metabolism has drawn attention in the recent years. In this study, we examined the polymorphism in the gene encoding the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR), namely, 677 C-T in women having Down syndrome (DS) children. MATERIALS AND METHODS: The prevalence of these variant genotypes (MTHFR 677 C-T polymorphism) in women having DS children (case mothers) (n = 110) was compared with controls (n = 111) from Punjab. Genotyping was done using the polymerase chain reaction method followed by restriction fragment length polymorphism. RESULTS: In the present study, 1.8% of case mothers had TT genotype while none of the control mothers showed this genotype. T allele frequency among cases was 0.13 and 0.11 in controls. The Chi-square value showed a non-significant difference between cases and controls. CONCLUSION: No association has been observed between 677 C-T polymorphism and risk of non-disjunction in case mothers. Detection of polymorphisms in more genes of folate pathway is required to find out the exact cause of non-disjunction.

Maternal MTHFR polymorphism (677 C–T) and risk of Down’s syndrome child: meta-analysis

Methylenetetrahydrofolate reductase (MTHFR) is the most important gene that participates in folate metabolism. Presence of valine instead of alanine at position 677 and elevated levels of homocystein causes DNA hypomethylation which in turn favours nondisjunction. In this study, we conducted a meta-analysis to establish link between maternal single-nucleotide polymorphism (SNP) and birth of Down’s syndrome (DS) child. A total of 37 case–control studies were selected for analysis including our own, in which we investigated 110 cases and 111 control mothers. Overall, the result of meta-analysis showed significant risk of DS affected by the presence of maternal SNP (MTHFR 677 C–T OR = 0.816, 95% CI = 0.741–0.900, P<0.0001). Heterogeneity of high magnitude was observed among the studies. The chi-square value suggested a highly significant association between homozygous mutant TT genotype and birth of DS child (χ2=23.63, P=0.000). Genetic models suggested that ‘T’ allele possesses high risk for DS whether present in dominant (OR = 1.23, 95% CI = 1.13–1.34); codominant (OR = 1.17, 95% CI = 1.10–1.25) or recessive (OR = 1.21, 95% CI = 1.05–1.38) form. The analysis from all 37 studies combined together suggested that MTHFR 677 C–T is a major risk factor for DS birth.

A Comparison of the Urothelial Cells and Cervix Scraping Techniques in the Screening Process for Cancer of the Cervix

Abstract Earlier detection of carcinoma of the cervix can achieve a goal of total or near total eradication of invasive carcinoma of the cervix bringing about sharp reductions in its incidence and mortality due to it. This has significance for Indian women where the incidence of the cancer and recognized risk factors are high. The Micronucleus assays in exfoliated bladder and cervical cells of women, coming to attention for gynaecological complications and subsequently diagnosed with cervix cancer, have been compared for specificity, sensitivity and efficiency. The test in cervix smears has better specificity and efficiency while the assay in urothelial cells has an edge over sensitivity. These tests, after validation, probably can assist as screening measures for cervix cancer in view of their simplicity, rapidity and cost-effectiveness as desired for population screening of risk groups.

Lowe Syndrome (Oculocerebrorenal Syndrome of Lowe): A Case Report of Two Brothers from India

Abstract Lowe syndrome (oculo-cerebro-renal syndrome of Lowe) is a rare X-linked recessive disorder characterized by the involvement of eyes, brain and kidneys. It is caused by the deficiency of enzyme phosphatidylinositol 4, 5-bisphosphate 5-phosphatase, which is required for the intracellular trafficking, second messengers and for the other aspects of cellular metabolism. The gene coding for this enzyme, OCRL1, has been localised at Xq25-q26.1 and mutations in it are reported to cause Lowe Syndrome. In this article we report two male siblings, from North India, with Lowe syndrome.