M. Sujatha

Non‐Robertsonian translocation t (2;11) is associated with infertility in an oligospermic man

Infertility is a major health problem which affects approximately 22% of married couples in reproductive age. Chromosomal defects are the most common genetic abnormalities in infertile men, with an incidence of cytogenetic abnormalities ranging from 2.1% to 15.5%. We describe here the clinical and cytogenetic studies carried out in a couple with repeated abortions. Cytogenetic analysis of the couple showed a de novo chromosomal translocation t (2;11)(p14;q21) in the male partner and a normal 46, XX karyotype in the female counterpart. Such an autosomal translocation may lead to the disruption of genes responsible for spermatogenesis or impaired synaptic complex pairing during meiosis resulting in reproductive failure.

De novo chromosomal translocation t(3;5)(q13;q35) in an infertile man

Chromosomal rearrangements are rare structural abnormalities that are usually associated with male infertility or sterility. We describe here the clinical and cytogenetic studies carried out in a couple with repeated abortions. Cytogenetic analysis of the male partner showed a de novo chromosomal translocation t(3;5)(q13;q35) which could be involved in the meiotic errors resulting in reproductive failure.

Mosaic triple X syndrome in a female with primary amenorrhea

BACKGROUND: Turners syndrome is the most common chromosomal abnormality in females, affecting 1 in 2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure. AIM: The aim of the study was to report a rare case of mosaic triple X syndrome in a female with primary amenorrhea. MATERIALS AND METHODS: The chromosomal analysis using GTG banding was carried out, which revealed a mosaicism with 45,XO/47,XXX chromosomal constitution. Fluorescent in situ hybridization was also carried out to further confirm the observation made in the study. CONCLUSION: The physical features presented by the female could be due to the 45,XO/47,XXX mosaicism and the karyotype analysis was consistent with the diagnosis and clinical symptoms. Triple X mosaicism was confirmed with conventional and molecular cytogenetic analysis.

Clinical and behavioural profile of a rare variant of Klinefelter syndrome-48, XXXY

Klinefelter’s syndrome is a sex chromosomal aneuploidy caused by an addition of X chromosome in males (47,XXY).Variants of this syndrome with X and Y polygamy are of rare occurrence. Here we describe a rare case of 48, XXXY Klinefelter’s variant from South India with a reported incidence of 1 per 17,000 to 1 per 50,000 male births. The presence of an extra X chromosome/s in these individuals has a great impact on the physical and cognitive functions, which could be attributed to gene dosage effects and genes involved in neurogenic development.

A functional polymorphism in the promoter region of interleukin-10 gene increases the risk for spontaneous abortions--a triad study.

PurposeSpontaneous abortion or miscarriage is the natural death of an embryo or foetus in the early stages of prenatal development. Interleukin-10 is an anti-inflammatory cytokine, produced by human cytotrophoblasts, and defects in its production result in specific pathological conditions during pregnancy. The present study is aimed to evaluate the association of IL-10 -1082G/A polymorphism in spontaneous abortions by comparing foetal, maternal and paternal groups—a triad study.MethodsA total of 50 families with spontaneous abortions and 60 families with medically terminated pregnancies were considered for the present study. DNA from foetal tissue and parental blood samples were extracted, and the genotype analysis of IL-10 -1082G/A promoter polymorphism was carried out by amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. A statistical analysis was applied to test for the significance of the results.ResultsThere was a statistically significant difference in the distribution of AA genotypes and A allele of IL-10 -1082G/A between the two family groups among foetuses (P = 0.0002) and mothers (P = 0.00005). The paternal group showed no significant difference in the genotype distribution of IL-10 between cases and controls.ConclusionIn conclusion, IL-10 G-1082A gene promoter polymorphism may act as a major genetic regulator in the etiology of spontaneous abortions.

Prenatal assessment of Three Rare Syndromes from Telangana region by 3D/4D Sonography

Ultrasound imaging serves as a powerful tool in the diagnosis of fetal anomalies. The three and four dimensional ultrasound scan overcomes some of the key limitations related to two-dimensional imaging. It facilitates detailed evaluation of suspected fetal abnormalities of face, neural tube, heart, skeletal and many subtle birth defects, which is pertinent to the pediatric surgeon for timely intervention. It also determines the age and developmental stage of the fetus, detects location and abnormalities of placenta, spot abnormal bleeding, ectopic pregnancies. The present article describes the three rare syndromes Meckel Gruber Syndrome, Holt Oram Syndrome (HOS) and Emanuel syndrome identified. During an attempt to screen a total of 3000 high risk pregnant women for the presence of congenital anomalies by 3D/4D sonography prenatally. Disruption of genes due to deletions and translocation are also identified which could be the putative candidate genes in the syndrome onset.

Transferrin (rs3811647) gene polymorphism in iron deficiency anemia

Background Iron-deficiency anemia (IDA) is the most common type of anemia, caused by inadequate iron availability for hemoglobin production due to the lack of dietary iron or insufficient uptake of iron. Transferrin (TF) exerts a crucial function in the maintenance of systematic iron homeostasis. The expression of the TF gene is controlled by transcriptional mechanism, although little is known about its influence on IDA. Hence, the aim of the current investigation was to determine the functional polymorphism (rs3811647) of TF gene in iron deficiency anemia. Material and Methods A total of 207 school children of age from 12-16 years were selected from Government High School Seetaphalmandi, Secunderabad, Andhra Pradesh and screened for iron deficiency. Out of which 70 school children had iron deficiency anemia with hemoglobin levels less than 11.5 g/dl and 137 were normal. Demographic details and blood samples were obtained from all the subjects. Genotyping was carried out by tetra-primer ARMS PCR followed by agarose gel electrophoresis, and appropriate statistical analysis. Results The genotype distribution of TF (rs3811647) region were 4.3% (AA), 81.4% (AG) and 14.3% (GG) in iron deficient children compared to 8% (AA), 72.3% (AG), and 19.7% (GG) in normal children. No significant variation was observed with respect to the allelic distribution [OD = 1.035 (0.67 – 1.59), p = 0.917] in the IDA group when compared to normal group. Conclusions There was no significant association of the TF (rs3811647) gene polymorphism with iron deficiency anemia. Thus, our study highlights the importance of other genetic variants influencing the outcome of iron deficiency anemia. However, larger samples have to be analyzed to confirm the same.

A 21/22 Translocation in a Female with Repeated Abortions: A Case Report

Abstract Robertsonian translocations (RT’s) are present in 0.1% of the general population and 1% of the infertile population. Two types of RT’s occur more frequently than all others, being 45,XX, rob(13;14)(q10;q10) and 45,XX, rob(14;21)(q10;q10) respectively. In the present report, an uncommon RT in a female with spontaneous repeated abortions is reported. Cytogenetic analysis of a couple with repeated abortions revealed the presence of 45,XX, rob(21;22)(q10;q10) chromosomal constitution in the female partner. The history of repeated abortions could be the outcome of unbalanced gametes (either monosomy or trisomy) resulting during the meiotic segregation of the balanced heterozygote female carrier.

Detection of L1 (CAM) mutations in X-linked mental retardation: A study from Andhra Pradesh, India

BACKGROUND : Mental health is an essential ingredient in the quality of life. Recent studies carried out in countries like Germany, USA, France, England and Belgium have provided evidence for the involvement of L1 (CAM) mutations in various X-linked mental retardation syndromes. L1 CAM is a neural cell adhesion molecule belonging to the superfamily of the immunoglobulins and is critical for proper CNS development in humans. AIM: This study was aimed to screen idiopathic mental retardation cases for L1 CAM mutations. MATERIALS AND METHODS : In this study, we screened 15 cases with mental retardation. Genomic DNA from the patients and control subjects was analyzed by polymerase chain reaction using specific primers. RESULTS : In 2 out of 15 patients, mutation was detected between exon 26 and 27. CONCLUSION : It is worthwhile to screen idiopathic mental retardation cases for L1 CAM mutations to reduce genetic morbidity in the population by offering genetic counseling and prenatal diagnosis.

Detection of L1 CAM mutation in a male child with mental retardation.

Recent studies have presented evidence for the involvement of L1CAM gene mutations in various X-linked mental retardation syndromes. The neural cell adhesion molecule, L1CAM is a transmembrane protein belonging to the super family of the immunoglobulins that play a key role in embryonic development of the nervous system and is involved in memory and learning. No studies were carried out from India on L1 CAM gene in X-linked mental retardation syndromes. Hence, an investigation was taken up to delineate the role of L1CAM gene in mental retardation.Two families (Family I and Family II) having only two members affected with mental retardation in each family were studied for mutations in L1CAM gene. In family II, the younger sibling showed deletion involving region between the nucleotide 13,773 (intron 25) and 14,158 (intron 27) region. The mutation what we observed in younger sibling of the family II is a novel mutation which was not hitherto reported in the world literature.