Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India.

Background: There is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India.

Methods: Data on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated.

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.

Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India.

World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated.

Genotypic analysis of SLC4A1 A858D mutation in Indian population associated with distal renal tubular Acidosis (dRTA) coupled with hemolytic anemia.

Introduction: Although distinctive, distal renal tubular acidosis (dRTA) and Hereditary Spherocytosis (HS) shares a common protein, the anion exchanger1 (AE1) encoded by SLC4A1gene. In spite of this, the co-existence of dRTA and HS has rarely been observed. To date, 23 mutations have been identified in SLC4A1 gene causing both autosomal recessive (AR) and autosomal dominant (AD) forms of dRTA.

Exosome as a Natural Gene Delivery Vector for Cancer Treatment.

Background: Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular environment by most of the cell types in-vivo and in-vitro. As a natural nanocarrier, exosomes are immunologically inert, biocompatible, and can cross biological barriers like the blood-brain barrier, intestinal barrier, and placental barrier.

Association of Thrombophilic Factors in Pathogenesis of Osteonecrosis of Femoral Head in Indian Population.

Purpose: Role of heritable blood clotting disorders, both thrombophilias and hypofibrinolysis in causing avascular necrosis (AVN) of femoral head have been studied in regions like Europe and U.S.A.

Differential response to FEIBA is strongly associated with the prothrombotic microparticles.

Background: Treatment of patients with hemophilia with an inhibitor is generally done using bypassing agents (BPA), wherein variability in response is observed. Due to lack of validated laboratory assays, monitoring is being carried out by clinical response only. Emerging biomarkers like procoagulant microparticles (MPs) may prove to be promising.

Mechanosensitive Piezo1 ion channel protein (PIEZO1 gene): update and extended mutation analysis of hereditary xerocytosis in India.

Hereditary xerocytosis (HX), also known as dehydrated stomatocytosis (DHSt) is a dominantly inherited genetic disorder exhibiting red cell membrane dehydration caused by the loss of the monovalent cation K and water. Variants in mechanosensitive Piezo ionic channels of the PIEZO1 gene are the primary cause of HX. We have utilized high throughput and highly precise next-generation sequencing (NGS) to make a diagnosis and examine the genotype-phenotype relationship in inflexible HX cases.

X-Linked Hyper IgM Syndrome Presenting with Recurrent Tuberculosis-a Case Report.

The hyper IgM syndromes are a group of rare primary immunodeficiency disorders. Currently 6 classes of HIGM are described. X-linked HIGM is also called the type 1 HIGM is the commonest variant in which children present in early infancy with features of combined immunodeficiency.

Applications of imaging flow cytometry in the diagnostic assessment of red cell membrane disorders.

Background: Red cell membranopathies refers to phenotypically and morphologically heterogeneous disorders. High throughput imaging flow cytometry (IFC) combines the speed, sensitivity, and phenotyping abilities of flow cytometry with the detailed imagery and functional insights of microscopy to produce high content image analysis with quantitative analysis. We have evaluated the applications of IFC to examine both the morphology as well as fluorescence signal intensity in red cell membranopathies.

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.

Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction.

Objectives: Glucose-6-phosphate isomerase (GPI) deficiency is an autosomal recessive genetic disorder causing hereditary non-spherocytic hemolytic anemia (HNSHA) coupled with a neurological disorder. The aim of this study was to identify GPI genetic defects in a cohort of Indian patients with HNSHA coupled with neurological dysfunction.

Methods: Thirty-five patients were screened for GPI deficiency in the HNSHA patient group; some were having neurological dysfunction.

Diagnostic challenges posed by a rare alpha globin chain variant Hb Fontainebleau in a pregnant female and its potential effects in her children in view of multiple globin gene defects in her husband.

Alpha globin chain variants per se do not cause severe morbidity and mortality but can modify - usually ameliorate - the clinical manifestations of beta globin chain variants when co-inherited with the latter. They also pose challenges in interpretation of high-performance liquid chromatography histograms and require molecular analysis for proper characterization. Hemoglobin (Hb) Fontainebleau is a rare alpha globin chain variant [alpha 21(B2) Ala→Pro], of which only three families have been reported from India in the past.

Lymphopenia and Severe Combined Immunodeficiency (SCID) - Think Before You Ink.

Objectives: Severe combined immunodeficiency (SCID) represents one of the most severe forms of Primary immunodeficiency (PID) disorders, characterized by T cell lymphopenia (TCL) and lack of cellular and humoral immune responses. However, not all patients with low T cell lymphocyte counts may have an abnormal T cell immunity and the observed TCL may be a temporary suppression resulting from transient lymphopenia secondary to severe infections. In such cases, it is necessary to estimate the severity of the observed TCL by assessing thymic capabilities.

Differential role of Kruppel like factor 1 (KLF1) gene in red blood cell disorders.

The master erythroid regulator KLF1,plays a pivotal role during erythroid lineage development by regulating the expression of many erythroid genes. Variations in the KLF1 gene are found to be associated with varied erythroid phenotypes. With the aim of determining the role of KLF1 gene variations in HbF induction and their genotype phenotype relationship, in this study, we screened 370 individuals with different hemoglobinopathy condition.

Molecular diagnosis of unexplained haemolytic anaemia using targeted next-generation sequencing panel revealed (p.Ala337Thr) novel mutation in GPI gene in two Indian patients.

Glucose-6-phosphate isomerase (GPI) deficiency is an autosomal recessive genetic disorder causing congenital haemolytic anaemia (CHA). Diagnosis of GPI deficiency by the biochemical method is unpredicted. Molecular diagnosis by identifying genetic mutation is the gold standard method for confirmation of disease, but causative genes involved in CHA are numerous, and identifying a gene-by-gene approach using Sanger sequencing is also cumbersome, expensive and labour intensive.