Comprehensive Study of Chromosomal Copy Number Variations and Genomic Variations Predicting Overall Survival in Myelodysplastic Syndromes.

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenia, marrow dysplasia and has a propensity to develop into acute myeloid leukemia. The disease progression is majorly affected by genetic defects. However, about 40-50% of patients with MDS present with a normal karyotype and develop different courses of disease.

Genomic and computational analysis of four novel variants of MPL gene in Congenital Amegakaryocytic Thrombocytopenia.

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, genetic, autosomal recessive disorder characterized by severe thrombocytopenia, due to inefficient bone marrow megakaryopoiesis eventually leading to aplasia. Majority of the cases are due to homozygous or compound heterozygous mutations in MPL gene encoding for thrombopoietin (THPO) receptor protein. CAMT can be diagnosed at early phase of life, with major complication of transfusion dependency and hematopoietic transplantation as only curative treatment.

Frequency and pattern of chromosomal abnormalities in acute myeloid leukemia from Western India: A retrospective study.

Context: Chromosomal abnormalities play an important role in diagnosis and prognosis of hematological diseases.

Aims: The aim of the present study was to study the pattern and frequency of chromosomal aberrations in acute myeloid leukemia (AML) subgroups from western India.

Settings And Design: A retrospective study was conducted through evaluating laboratory proforma which were filled during 2005 to 2014 for diagnosis and treatment of AML subjects.

Synergetic effect of Azacitidine and Sorafenib in treatment of a case of myeloid neoplasm with sole chromosomal abnormality t(8;22)(p11.2;q11.2)/BCR-FGFR1 rearrangement.

The sole t(8;22)(p11.2;q11.2)/BCR- FGFR1 chromosomal abnormality formerly known as aCML is an extremely rare disease entity with a history of rapid progression.

Comprehensive molecular analysis identifies eight novel variants in XY females with disorders of sex development.

Disorders of sex development (DSD) are a group of clinical conditions with variable presentation and genetic background. Females with or without development of secondary sexual characters and presenting with primary amenorrhea (PA) and a 46,XY karyotype are one of the classified groups in DSD. In this study, we aimed to determine the genetic mutations in 25 females with PA and a 46,XY karyotype to show correlations with their phenotypes.

Over expression of mTOR gene predicts overall survival in myelodysplastic syndromes.

Background: Myelodysplastic syndromes (MDS) is defined as heterogenous disease, it contains heterogenous leukemic stem cells with various degree of cell differentiation. The perturbation of genes involved in myeloid progenitor cell growth, differentiation and proliferation lead to morphologic dysplasia, maturation arrest, ineffective hematopoiesis hence the cytopenias and propensity to develop into acute myeloid leukemia (AML). Heterogeneous subsets of MDS patients have been defined by their clinical and biologic abnormalities.

Comprehensive analysis of genetic factors predicting overall survival in Myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of clonal hematological disease with high risk of progression to AML. Accurate risk stratification is of importance for the proper management of MDS. Genetic lesions (Cytogenetic and Molecular mutations) are known to help in prognosticating the MDS patients.

Novel deletion of exon 3 in TYR gene causing Oculocutaneous albinism 1B in an Indian family along with intellectual disability associated with chromosomal copy number variations.

Background: Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypo-pigmentation of skin, hair, and eyes. The OCA clinical presentation is due to a deficiency of melanin biosynthesis. Intellectual disability (ID) in OCA cases is a rare clinical presentation and appropriate diagnosis of ID is challenging through clinical examination.

A comprehensive molecular study identified 12 complementation groups with 56 novel FANC gene variants in Indian Fanconi anemia subjects.

Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA.

Assessment of Long-Term in vitro Multiplied Human Wharton's Jelly-Derived Mesenchymal Stem Cells prior to Their Use in Clinical Administration.

The quantity of mesenchymal stem/stromal cells (MSCs) required for a particular therapy demands their subsequent expansion through ex vivo culture. During in vitro multiplication, they undergo replicative senescence which may alter their genetic stability. Therefore, this study was aimed to analyze cellular, molecular, and chromosomal alterations in Wharton's jelly-derived MSCs (WJ-MSCs) during their in vitro sequential passages, where WJ-MSCs were sequentially passaged up to P14 and cells were evaluated at an interval of P2, P6, P10, and P14.

Nitric oxide synthase-2 (NOS2) gene polymorphism c.1832C>T (Ser608Leu) associated with nitrosative stress in Fanconi anaemia.

Fanconi anemia (FA) occurs due to genomic instability with predisposition to bone marrow failure, phenotypic abnormalities and cancers. Though mutations in 22 genes leading to DNA repair defect have been identified, the cellular factor such as oxidative stress has also shown to be associated with FA. Nitrosative Stress (NS) is biochemically correlated to many oxidative stress related disorders and the NS as a pathological hallmark in FA has been so far overlooked.

Severe telomere shortening in Fanconi anemia complementation group L.

Fanconi Anemia (FA) is a rare genetic disease with the incidence of 1 in 360,000 and is characterised by bone marrow failure, physical abnormalities, pancytopenia, and high frequency of chromosomal breakage and increased risk of evolving into malignancy. Telomere plays an important role in genomic stability, ageing process and cancers. Telomere shortening has been reported in FA.

array-CGH revealed gain of Yp11.2 in 49,XXXXY and gain of Xp22.33 in 48,XXYY karyotypes of two rare klinefelter variants.

Klinefelter syndrome (KS) variants often share common features with classical syndrome but some of these variants present with a distinct phenotype. The incidence of sex chromosome tetrasomy and pentasomy are very less and generally diagnosed after prepubertal age. The early diagnosis of complex and unclassified syndromes and it's correlation with genotype is necessary for personalized treatment as well as genetic counselling of the affected families.

Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia.

In-vitro studies with different Fanconi anemia (FA) cell lines and FANC gene silenced cell lines indicating involvement of mitochondria function in pathogenesis of FA have been reported. However, in-vivo studies have not been studied so far to understand the role of mitochondrial markers in pathogenesis of FA. We have carried out a systematic set of biomarker studies for elucidating involvement of mitochondrial dysfunction in disease pathogenesis for Indian FA patients.

A founder variant in the South Asian population leads to a high prevalence of FANCL Fanconi anemia cases in India.

Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure, predisposition to cancer, and congenital abnormalities. FA is caused by pathogenic variants in any of 22 genes involved in the DNA repair pathway responsible for removing interstrand crosslinks. FANCL, an E3 ubiquitin ligase, is an integral component of the pathway, but patients affected by disease-causing FANCL variants are rare, with only nine cases reported worldwide.

Chromosomal Aberrations in Primary Amenorrhea: A Retrospective Study.

Objectives: The aim of this study was to estimate the frequency of chromosomal abnormalities and establish the association with clinical of factors such as secondary sexual characters and gonad development in primary amenorrhea (PA).

Study Design: The study was carried out in a large cohort of PA. The chromosomal aberrations were correlated with secondary sexual characters and anatomical abnormalities.

Lack of association between functional polymorphism of DNA repair genes (XRCC1, XPD) and clinical response in Indian chronic myeloid leukemia patients.

The resistance for the tyrosine kinase inhibitors in chronic myeloid leukemia (CML) occurs mainly due to BCR/ABL1 dependent and independent mechanisms. The defective DNA repair due to functional polymorphisms in DNA repair genes, might act as an etiological factor for leukemia progression. The study was carried out to understand the role of DNA repair genes (XRCC1, XPD) polymorphisms in Imatinib mesylate (IM) resistant CML patients.

Natural Killer Cell Degranulation Defect: A Cause for Impaired NK-Cell Cytotoxicity and Hyperinflammation in Fanconi Anemia Patients.

Fanconi anemia (FA) is a rare inherited syndrome characterized by progressive bone marrow failure (BMF), abnormal skin pigmentation, short stature, and increased cancer risk. BMF in FA is multifactorial and largely results from the death of hematopoietic stem cells due to genomic instability. Also, inflammatory pathology in FA has been previously reported, however the mechanism is still not clear.

Partial trisomy 9 (9pter->9q22.1) and partial monosomy 14 (14pter- >14q11.2) due to paternal translocation t(9;14)(q22.1;q11.2) in a case of Dysmorphic features.

Trisomy 9 including mosaic and partial trisomy is less frequently seen chromosomal abnormality in live born children. The pure or partial trisomy 9 frequently been reported in prenatal diagnosis and product of conception. However few studies reported partial trisomy 9 in live born children.

Centrosome Aberration Frequency and Disease Association in B-Acute Lymphoblastic Leukemia.

Recent developments in genome-wide genetic analysis in B-acute lymphoblastic leukemia (B-ALL) have provided insight into disease pathogenesis and prognosis. B-ALL cases usually carry a primary genetic event, often a chromosome translocation, and a constellation of secondary genetic alterations that are acquired and selected dynamically in a nonlinear fashion. As far as we are aware of, for the first time, we studied centrosome aberration in patients with B-ALL to understand the progression of the disease.