Acquired von Willebrand syndrome: a rare disorder of heterogeneous etiology.

Context: Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that mimics the inherited form of von Willebrand disease (VWD) in terms of laboratory findings and clinical presentation.

Aims: To study the etiology of acquired VWD.

Settings And Design: The patients referred from various hospitals in and out of Mumbai were included in the study.

A novel 5-way translocation t(9;11;13;19;22) in a case of chronic-phase chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder that occurs because of t(9;22)(q34;q11) translocations. Complex translocations have been reported in CML. We report a novel 5-way translocation 46,XY,t(9;11;13;19;22)(9q34.

Influence of CYP2C9 and VKORC1 gene polymorphisms on warfarin dosage, over anticoagulation and other adverse outcomes in Indian population.

The aim of this study was to determine the frequencies of SNPs in the vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes and their effect on warfarin dose requirement, over anticoagulation and other adverse outcomes in Indian population. A total of 145 warfarin treated patients for various clinical conditions were screened for VKORC1 and CYP2C9 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We found that homozygous VKORC1-1639 AA and CYP2C9 (*)3/(*)3 polymorphisms showed 100% association with risk of over anticoagulation and other adverse events.

Detection of fetal mutations causing hemoglobinopathies by non-invasive prenatal diagnosis from maternal plasma.

Background: Prenatal diagnosis of hemoglobinopathies enables couples at risk to have a healthy child. Currently used fetal sampling procedures are invasive with some risk of miscarriage. A non-invasive approach to obtain fetal deoxyribonucleic acid (DNA) for diagnosis would eliminate this risk.

Variable presentation of HB H disease due to homozygosity for the rare polyadenylation signal A T(Indian) (AATAAA>AATA- -) mutation in four Indian families.

The aim of this study was to identify the molecular defects leading to the variable clinical and hematological presentation of four patients with Hb H disease. Investigations included a complete blood count, high performance liquid chromatography (HPLC) analyses, cellulose acetate electrophoresis (pH 8.9), heat stability test, α genotyping by multiplex gap polymerase chain reaction (gap-PCR) to screen for the eight common α-globin gene deletions and DNA sequencing to detect the other deletional and nondeletional α-globin gene mutations.

Spectrum of hemoglobinopathies among the primitive tribes: a multicentric study in India.

We evaluated the spectrum of hemoglobinopathies among the primitive tribal groups from 4 states in India. A total of 15,200 individuals from 14 primitive tribal groups were studied by automated high-performance liquid chromatography. The hemoglobin S (HbS) allele frequency varied from 0.

Effect of Cis Acting Potential Regulators in the β Globin Gene Cluster on the Production of HbF in Thalassemia Patients.

The clinical presentation of β-thalassemia intermedia phenotypes are influenced by many factors. The persistence of fetal hemoglobin and several polymorphisms located in the promoters of γ- and β-globin genes are some of them. The aim of this study was to evaluate the combined effect of the -158 Gγ (C→T) polymorphism and of the (AT)x(T)y configuration, as well as their eventual association with elevated levels of HbF in β-thalassemia carriers, β-thalassemia intermedia, β-thalassemia major and normal controls of Indian origin.

Role of microparticles in recurrent miscarriages and other adverse pregnancies: a review.

The multiple functions attributed to microparticles (MPs) include blood coagulation, inflammation, tumorigenesis, angiogenesis, immunomodulatory functions and intercellular cross talk. These have drawn considerable interest during the last few years. The prothrombotic nature of MPs has linked them with almost all groups of thrombotic disorders including recurrent miscarriage (RM) and other abnormal pregnancy outcomes.

Acquired and Heritable Thrombophilia in Indian Patients With Pediatric Deep Venous Thrombosis (DVT).

Deep venous thrombosis (DVT) in children is more often associated with underlying pathological conditions than with hereditary thrombophilia. The present study is a retrospective analysis of thrombophilia in 285 pediatric patients with venous thrombosis at different sites. Four common thrombophilia markers, that is protein C, protein S, antithrombin III, and factor V Leiden (FVL) mutation, were analyzed.

Identification of a novel large intragenic deletion in a family with Fanconi anemia: first molecular report from India and review of literature.

We report here an Indian case with Fanconi anemia (FA) presented with fever, pallor, short stature, hyperpigmentation and upper limb anomaly. Chromosome breakage analysis together with FANCD2 Western blot monoubiquitination assay confirmed the diagnosis as FA. Multiplex ligation-dependent probe amplification (MLPA) revealed a novel homozygous large intragenic deletion (exons 8-27 del) in the FANCA gene in the proband.

Effect of a group of genetic markers around the 5' regulatory regions of the β globin gene cluster linked to high HbF on the clinical severity of β thalassemia.

The clinical and hematological course of β thalassemia intermedia is influenced by a number of genetic factors which play a role in increasing fetal haemoglobin levels. Several polymorphisms located in the promoters of β and γ globin gene are involved in influencing the disease severity. Our objective was to study the effect of cis-DNA haplotypes, motifs, or polymorphisms (Pre G γ globin gene haplotypes, Aγ-δ intergenic region haplotypes XmnI and (AT)(x)(T)(y) polymorphisms, β-LCR HS2 and HS3 site motifs) that may contribute to higher HbF levels and a milder clinical course.

UDP-glucuronosyltransferase 1A1 (UGT1A1) gene haplotypes and their effect on serum bilirubin concentration in healthy Indian adults.

The aim of the present study was to investigate the allele and genotype frequencies and haplotype structures of the variants in the UGT1A1 gene and their association with serum bilirubin levels in healthy adults. Total serum bilirubin levels were measured in 300 healthy adults (normal hematology and liver function test) and genotyping of seven SNPs was performed by PCR-RFLP, Gene Scan analysis and direct sequencing on the ABI Prism 310 Genetic Analyzer. Of the seven SNPs, four were found to be polymorphic and the frequencies of minor alleles were 0.

Prevalence of β-thalassemia and other haemoglobinopathies in six cities in India: a multicentre study.

The population of India is extremely diverse comprising of more than 3,000 ethnic groups who still follow endogamy. Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. The data on the prevalence of β-thalassemias and other haemoglobinopathies in different caste/ethnic groups of India is scarce.

SRY sequence in maternal plasma: Implications for non-invasive prenatal diagnosis: First report from India.

Aim: The presence of circulatory cell-free fetal DNA in maternal plasma has found new applications in non-invasive risk-free prenatal diagnosis.

Materials And Methods: We made use of a size separation approach along with real time polymerase chain reaction (PCR) to evaluate the use of fetal DNA in the detection of the sex of the fetus. Cell-free fetal DNA was isolated from the plasma of 30 women (10-20 weeks gestation) using a size separation approach.

Compromising for carrier detection of beta thalassemia based on measurement of HbA2 levels in unusual cases.

Background: An increased HbA2 level is the hallmark for identification of β thalassemia carriers. However, in some carriers the level of HbA2 is not typically elevated creating difficulties in making a diagnosis.

Methods: We describe a family having an affected child referred to us for confirmation of diagnosis of β thalassemia.

HLA-DRβ1*04 typing by simple in-house PCR-SSP technique for rheumatoid arthritis patients.

A strong association between rheumatoid arthritis (RA) and human leukocyte antigen (HLA) has been observed in many different populations and that accounts for approximately one-third of the genetic component of RA susceptibility. The greatest effect comes from DRβ1 gene where the strongest association has been found with DRβ1*04 (DR4) allele. As serology has some disadvantages over polymerase chain reaction (PCR)-based techniques and commercially available PCR-based kits are expensive, this study was aimed to standardize simple in-house PCR-SSP technique.

Hereditary protein C deficiency in Indian patients with venous thrombosis.

Approximately, 4-11 % of the patients with idiopathic venous thrombosis (VT) show protein C (PC) deficiency. The molecular pathology of PC deficiency was analyzed in 102 patients; 98 healthy controls were also studied to assess the association of various polymorphisms with reduced PC levels. PROC gene mutations were detected only in 8 (7.

De novo origin of multiple small supernumerary marker chromosomes (sSMCs) in a child with intellectual disability and dysmorphic features.

Small supernumerary marker chromosomes (sSMCs) are a heterogeneous group with regards to their clinical effects as well as their chromosomal origin and their shape. The sSMCs are associated with mental retardation and dysmorphic features. Multiple sSMCs are rarely reported.