Prospective Case-Control Study to Evaluate the Role of Glutathione S Transferases (GSTT1 and GSTM1) Gene Deletion in Breast Carcinoma and Its Prognostic Significance.

Breast cancer is the most common cause of cancer death in women with the incidence rising in young women. GST gene polymorphisms are significant because of their role in the detoxification of both environmental carcinogens and also cytotoxic drugs used in therapy for breast cancer. The present study has been designed to identify the role of polymorphisms in GSTT1 and GSTM1 genes in the risk of development of breast cancer, in the prognostication of breast cancer, and in the prediction of response towards chemotherapy.

Diagnostic role of conventional cytogenetics and fluorescence in situ hybridization (FISH) in chronic myeloid leukemia patients.

Introduction: The limitation of cytogenetic analysis is that the Ph chromosome cannot be detected in clumped metaphase or in interphase cells. Fluorescence in situ hybridization (FISH) is a highly sensitive molecular genetic technique, which enables to detect break point cluster region--Abelson (BCR-ABL) complex and minimal residual disease in all Ph positive CML patients not only in metaphase but also in interphase cells.

Aims: To detect Ph chromosome in CML patients by the use of conventional cytogenetics and FISH.

Fertility among women with classical congenital adrenal hyperplasia: report of seven cases where treatment was started after 9 years of age.

Background And Aim: Androgen excess is believed to be one of the major factors responsible for poor fertility outcomes in females with congenital adrenal hyperplasia (CAH). Some believe that the adverse effect of androgens on fertility could have its origins as early as the antenatal years. To assess the impact of prolonged androgen exposure on fertility in CAH patients, we compiled the data of females with CAH followed in our clinic during the last 25 years who were sexually active and had not been initiated on steroids until age 9 years.

Gender identity of children and young adults with 5alpha-reductase deficiency.

Male pseudohermaphroditism (46,XY DSD) due to 5alpha-reductase deficiency has been recognized for the last few decades. There is scant literature on this entity in India. We compiled data on five patients with this disorder.

Screening for Y-chromosome microdeletions in infertile Indian males: utility of simplified multiplex PCR.

Background & Objective: Analysis of the microdeletions in the azoospermia factor (AZF) region of Y chromosome by PCR is an important screening tool in the work-up of infertile males opting for assisted reproductive techniques. In the present study, the Y chromosome microdeletions were analyzed by PCR using primers corresponding to 16 sequence tagged sites (STS) and three genes of the AZF region in infertile Indian men. Feasibility of developing a simplified multiplex PCR for screening of the Y chromosome microdeletions has been explored.

Molecular diagnosis of 5alpha-reductase-2 gene mutation in two Indian families with male pseudohermaphroditism.

Aim: To identify the genotype of two Indians with male pseudohermaphroditism.

Methods: Standard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carried out for diagnosing the genetic sex in these subjects with genital ambiguity.

Higher frequency of Yq microdeletions in sperm DNA as compared to DNA isolated from blood.

Aim: To determine if Yq microdeletion frequency and loci of deletion are similar in two tissues (blood and sperm) of different embryological origin.

Methods: The present study included 52 infertile oligozoospermic cases. In each case, DNA was isolated from blood and sperms and polymerase chain reaction (PCR) microdeletion analysis was done from genomic DNA isolated from both the tissues.

A 2-year-old baby with Downs syndrome, cryptorchidism and testicular tumour.

Seminomas are rare germ cell tumours. It occurs usually in men aged over 50 years. Seminomas differ genetically and clinically from germ cell tumours.

Role of testicular fine-needle aspiration cytology in infertile men with clinically obstructive azoospermia.

Background: Azoospermia due to obstruction of the vaso-epididymal junction is one of the few surgically correctable causes of male infertility. In patients where all clinical and laboratory parameters suggest a vaso-epididymal junction block amenable to surgery, failure to find normal spermatogenesis on fine-needle aspiration cytology (FNAC) of the testis may necessitate a change in treatment modality to the more expensive intracytoplasmic sperm injection. We evaluated the validity of FNAC findings in predicting failure of surgical exploration when clinical parameters suggest otherwise.

Cytogenetic and molecular analysis of male infertility: Y chromosome deletion during nonobstructive azoospermia and severe oligozoospermia.

Reduced male fertility and subfertility can be caused by genetic factors that affect both germ cell development, differentiation, and function; in particular, chromosome abnormalities and Yq microdeletions are a possible cause of spermatogenetic impairment in males as shown by their higher frequency in infertile men than in the general male population. Microdeletion of the long arm of the Y chromosome (Yq) are associated with spermatogenic failure and have been used to define three regions on Yq (AZFa, AZFb, and AZFc) that are critical for germ cell development. With the advent of assisted reproductive technology and intracytoplasmic sperm injection, knowledge about the various factors leading to spermatogenic impairment is one of the most important aspects of scientific research.

Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome.

Aim: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS).

Methods: Blood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines.

Conservation of the RB1 gene in human and primates.

Mutations in the RB1 gene are associated with retinoblastoma, which has served as an important model for understanding hereditary predisposition to cancer. Despite the great scrutiny that RB1 has enjoyed as the prototypical tumor suppressor gene, it has never been the object of a comprehensive survey of sequence variation in diverse human populations and primates. Therefore, we analyzed the coding (2,787 bp) and adjacent intronic and untranslated (7,313 bp) sequences of RB1 in 137 individuals from a wide range of ethnicities, including 19 Asian Indian hereditary retinoblastoma cases, and five primate species.

Yq microdeletions--azoospermia factor candidate genes and spermatogenic arrest.

In the last few years considerable progress has been made in the study of sperm physiology and the biology of gamete interaction, furthering our understanding of the pathophysiology of male infertility. With the advent of assisted reproductive technology and intracytoplasmic sperm injection, study of the various factors leading to spermatogenic impairment has become a major focus of scientific research. Understanding the genetic factors that lead to infertility has taken on a certain urgency, as we have learned not only of the transmission to male offspring of spermatogenic impairment, but that these offspring may also be born with a secondary, larger deletion with worsening of phenotype and genital ambiguity.

Nongonadal neoplasia in patients with Turner syndrome.

In a prospective study of 50 patients with retinoblastoma, a 10-year-old girl with unilateral (right eye) retinoblastoma was found to have 45,X karyotype. Because there is increasing evidence of nongonadal neoplasia occurring in patients with Turner syndrome in addition to the gonadal tumor from dysgenetic gonads, we reviewed the occurrence of nongonadal neoplasia in Turner syndrome cases. Of all the nongonadal neoplasia, neurogenic tumors show a preponderence among children and young adults with Turner syndrome.

Imaging in intersex disorders.

Background: Evaluation of the gonads and internal genital structures is an essential component for evaluation of patients presenting with ambiguous genitalia. Ultrasonography (US) and magnetic resonance imaging (MRI) are the two preferred modalities.

Objective: To compare US and MRI in patients with intersex for localization of gonads and internal genitalia.

Differentiation of Fanconi anemia from idiopathic aplastic anemia by induced chromosomal breakage study using mitomycin-C (MMC).

This study was conducted to differentiate between Fanconi anemia (FA) and "idiopathic" aplastic anemia on the basis of induced chromosomal breakage study with mitomycin C (MMC). MMC-stress test was conducted on peripheral blood lymphocytes from 29 patients with aplastic anemia. Ten patients with very high percentage of chromosomal breakage and four patients exhibiting somatic mosaicism were diagnosed as FA on the basis of chromosomal breakage study.

14q(22) deletion in a familial case of anophthalmia with polydactyly.

We report a family of anophthalmia with ocular and extraocular manifestations. The proband, his three sisters, and two sons had anophthalmia and preaxial polydactyly in the right hand. Cytogenetic analysis was done for the proband and two of his sons, one of whom was affected.

Molecular screening for Yq microdeletion in men with idiopathic oligozoospermia and azoospermia.

Infertility affects 15% couples attempting pregnancy and in 40-50% of these cases the male partner has qualitative or quantitative abnormalities of sperm production. Microdeletions in the azoospermia factor (AZF) region on the long arm of the Y chromosome are known to be associated with spermatogenic failure and have been used to define three regions on Yq (AZFa, AZFb and AZFc) which are critical for spermatogenesis and are recurrently deleted in infertile males. Semen analysis was carried out on one hundred and twenty five infertile males with oligozoospermia and azoospermia.

A case of chronic myeloid leukemia complicated with minimal change nephrotic syndrome.

We present a 28-year-old patient with chronic myeloid leukemia (CML) in chronic phase complicated with nephrotic syndrome. The bone marrow cells revealed the presence of Philadelphia chromosome, the cytogenetic hallmark of CML, that results from a balanced, reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11). This reciprocal translocation leads to the formation of the BCR/ABL fusion gene, the presence of which was confirmed using the highly sensitive fluorescence in situ hybridization technique.

Spermatogenic arrest in men with testicular hyperthermia.

Sperm is produced by a highly complex and poorly understood differentiation process known as spermatogenesis. Occupational exposure to high temperatures adversely affect testicular function, causing partial or complete spermatogenic arrest. Dyers, cooks, blast furnace workers, and men with varicocele are known to develop testicular hyperthermia, which leads to oligoasthenoteratozoospermia (OAT) and azoospermia.

Human molecular cytogenetics: diagnosis, prognosis, and disease management.

The year 2001 witnessed the sequencing of 90% of the euchromatic region in the human genome but the ultimate goal to delineate the positions of all genes is yet to be achieved. Fluorescence In Situ Hybridization (FISH) is one of the methods for localizing genes on chromosomes. In the present study, diagnostic utility of single-, dual-, and multicolor FISH was evaluated for prenatal diagnosis, cancer genetics, and screening of various congenital anomalies (sex chromosomal and autosomal).

AZF microdeletions associated with idiopathic and non-idiopathic cases with cryptorchidism and varicocele.

Aim: To identify submicroscopic interstitial deletions in azoospermia factor (AZF) loci in idiopathic and non-idiopathic cases of male infertility in Indians.

Methods: One hundred and twenty two infertile males with oligozoospermia or azoospermia were included in this study. Semen analysis was done to determine the sperm density, i.

Evaluation of minimal residual disease in patients with chronic myeloid leukaemia on IFN-alpha 2b therapy using conventional cytogenetics and fluorescence in situ hybridization.

Background: Chronic myeloid leukaemia (CML) is a haematopoietic malignancy characterized by the presence of the Philadelphia (Ph) chromosome that results from balanced reciprocal translocation between chromosomes 9 and 22 leading to the formation of the bcr/abl fusion gene. Studies have shown that interferon-alpha (IFN-alpha) therapy induces both cytogenetic (reduction in Ph+ cells) and molecular response (reduction in the bcr/abl positive cells) in a large proportion of patients, thereby improving their prognosis and survival. There are no reports available from India on the clinical management of CML patients using IFN-alpha therapy and molecular methods for the evaluation of residual disease.