Clinical and laboratory evaluation of idiopathic male infertility in a secondary referral center in India.

The genetic basis of infertility has received increasing recognition in recent years, particularly with the advent of assisted reproductive technology. It is now becoming obvious that genetic etiology for infertility is an important cause of disrupted spermatogenesis. Y-chromosome microdeletions and abnormal karyotype are the two major causes of altered spermatogenesis. To achieve biological fatherhood, intracytoplasmic sperm injection (ICSI) is performed in cases of severe infertility with or without genetic abnormalities. There is a concern that these genetic abnormalities can be transmitted to the male progeny, who may subsequently have a more severe phenotype of infertility. A total of 200 men were recruited for clinical examinations, spermiograms, hormonal profiles, and cytogenetic and Yq microdeletion profiles. Testicular biopsy was also performed whenever possible and histologically evaluated. Genetic abnormalities were seen in 7.1% of cases, of which 4.1% had chromosomal aberrations, namely Klinefelter's mosaic (47XXY) and Robertsonian translocation, and 3.0% had Yq microdeletions, which is very low as compared to other populations. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were significantly increased in men with nonobstructive azoospermia (NOA) as compared to severe oligoasthenozoospermia (P<0.0001), whereas testosterone levels were significantly decreased in men with microdeletions as compared to men with no microdeletions (P<0.0083). Low levels of androgen in men with microdeletions indicate a need to follow-up for early andropause. Patients with microdeletions had more severe testicular histology as compared to subjects without deletions. Our studies showed a significant decrease (P<0.002) in the serum inhibin B values in men with NOA, whereas FSH was seen to be significantly higher as compared to men with severe oligoasthenozoospermia (SOAS), indicating that both the Sertoli cells as well the germ cells were significantly compromised in cases of NOA and partially affected in SOAS. Overall inhibin B in combination with serum FSH would thus be a better marker than serum FSH alone for impaired spermatogenesis. In view of the genetic and hormonal abnormalities in the group of infertile men with idiopathic severe oligozoospermia and NOA cases, who are potential candidates for ICSI, genetic testing for Y-chromosome microdeletions, karyotype, and biochemical parameters is advocated.

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 to de 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 a de 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 a de novo event of i(18p) 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.

Validity of analysis of FMRP expression in blood smears as a screening test for Fragile X Syndrome in the Indian population.

Molecular diagnosis of Fragile X Syndrome (FXS) is carried out by PCR or Southern blot analysis on DNA isolated from leukocytes. These DNA analyses are time consuming and expensive, making it impractical for mass screening programs. We have recently standardized and tested the diagnostic potential of a rapid antibody test on blood smears, based on the presence of FMRP, the protein product of the FMR1 gene, in lymphocytes from normal individuals and the absence of FMRP in lymphocytes in patients with FXS. This test is essentially similar to the one developed at Erasmus University in the Netherlands, with suitable modifications. The diagnostic power of the antibody test is perfect for males, whereas the results are less specific for females. The cutoff value for affected male individuals, expressed as the percentage of FMRP-positive cells, was 20%. In normal individuals, the cutoff value was 85%. The results of the antibody test correlated well with that of Southern blots. Sensitivity of the test was 100% and specificity was 97.5%. This noninvasive test requires one or two drops of blood and is rapid, simple, and cheap, making it an ideal choice for large screening large groups of male mental retardates and neonates for FXS in developing countries such as India.

Beta-thalassaemia carrier detection by ELISA: a simple screening strategy for developing countries.

The frequency of beta-thalassaemia in India ranges from 3.5% to 15% in the general population and of the 100,000 children born with thalassaemia major in the world, 10,000 are in India alone. Affected children do not die immediately, but treatment by regular transfusion is costly and leads to iron overload and death. Therefore, health services in lower-economic countries can sustain patients only if the numbers can be limited. Detecting carrier couples by simple blood test can prevent thalassaemia and at-risk couples can be identified and informed of their genetic risk before having children. A prevention programme including population screening, counselling, and prenatal diagnosis will markedly reduce the birth prevalence of affected individuals. Hemoglobin A2 (HbA2) measurement in human hemolysates has great significance, since its level can indicate beta-thalassaemia carrier status in otherwise healthy individuals. We have developed a rapid, simple, and inexpensive enzyme linked immunosorbent assay (ELISA) for the quantitation of HbA2, which can be used in carrier screening programmes in developing countries like India. In a limited trial for beta-thalassaemia carrier screening, the results obtained with ELISAs were compared with those obtained with the microcolumn chromatography method (r = 0.89).

Tel-Hashomer camptodactyly syndrome with hirsuitism in an Indian family.

Two new cases with the Tel-Hashomer camptodactyly syndrome have been ascertained in an Indian family. This report emphasizes the autosomal recessive nature of disease and documents an additional feature of hirsuitism not previously described. The gene for Tel-Hashomer camptodactyly syndrome is present in all populations around the world.