Development of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies.

Ex vivo cellular system that accurately replicates sickle cell disease and β-thalassemia characteristics is a highly sought-after goal in the field of erythroid biology. In this study, we present the generation of erythroid progenitor lines with sickle cell disease and β-thalassemia mutation using CRISPR/Cas9. The disease cellular models exhibit similar differentiation profiles, globin expression and proteome dynamics as patient-derived hematopoietic stem/progenitor cells.

Scalable noninvasive amplicon-based precision sequencing (SNAPseq) for genetic diagnosis and screening of β-thalassemia and sickle cell disease using a next-generation sequencing platform.

β-hemoglobinopathies such as β-thalassemia (BT) and Sickle cell disease (SCD) are inherited monogenic blood disorders with significant global burden. Hence, early and affordable diagnosis can alleviate morbidity and reduce mortality given the lack of effective cure. Currently, Sanger sequencing is considered to be the gold standard genetic test for BT and SCD, but it has a very low throughput requiring multiple amplicons and more sequencing reactions to cover the entire HBB gene.

A Simple, Cost-Effective, and Extraction-Free Molecular Diagnostic Test for Sickle Cell Disease Using a Noninvasive Buccal Swab Specimen for a Limited-Resource Setting.

Sickle cell disease (SCD) is the most prevalent life-threatening blood monogenic disorder. Currently, there is no cure available, apart from bone marrow transplantation. Early and efficient diagnosis of SCD is key to disease management, which would make considerable strides in alleviating morbidity and reducing mortality.

Detection of c.139G>A (D47N) mutation in gene in an extended family with inheritance of autosomal dominant zonular cataract without pulverulent opacities by exome sequencing.

The aim of this studywas to identify the gene causing bilateral autosomal dominant zonular congenital cataract (ADZCC) without pulverulent opacities in an extended Muslim family by exome sequencing and subsequent analysis. An extended family of 37 members (14 affected and 23 unaffected) who belong to different nuclear families was screened for causative gene. Proband and her unaffected son were screened for causative variant by exome sequencing followed by Sanger sequencing of the proband's entire nuclear family.

Haplotype association and synergistic effect of human aldosterone synthase (CYP11B2) gene polymorphisms causing susceptibility to essential hypertension in Indian patients.

Background: Aldosterone synthase (CYP11B2) is a key enzyme involved in the terminal steps of aldosterone biosynthesis. Genetic variability in CYP11B2 gene has been associated with heterogeneous aldosterone production, which can affect sodium homeostasis and thereby regulation of blood pressure. Hence, the present study was aimed to explore the single-locus variations, haplotype and epistasis patterns of CYP11B2 (C-344T, intron-2 gene conversion and Lys173Arg) gene polymorphisms, and the risk contributed by them to the development of essential hypertension (EHT).

Role of tagged SNPs of the AGT gene in causing susceptibility to essential hypertension.

Aim: Angiotensinogen (AGT) is one of the candidate genes that has been extensively investigated for association of its variants with essential hypertension. Studies focusing on the contribution of tagged single nucleotide polymorphisms (SNPs) in the AGT gene are limited and lacking from Indian population. Hence, the present study was carried out to examine the role of five tagged SNPs viz.

Evaluation of leptin and leptin receptor gene 3' UTR polymorphisms in essential hypertension.

Introduction: Leptin and leptin receptor gene polymorphisms have been associated with obesity; however, their association with blood pressure has not been fully elucidated. The aim of this study was to examine the effect of tetranucleotide repeat polymorphism in the 3' flanking region of the leptin and leptin receptor gene on blood pressure in hypertensives with obesity.

Methods: Two hundred and eighty hypertensives and 200 healthy controls were analyzed for a tetranucleotide repeat polymorphism of leptin and leptin receptor genes.

Novel mutations affecting the secondary structure of MT-RNR1 gene: a causal relationship with profound nonsyndromic hearing impairment.

Mutations in mitochondrial DNA (mtDNA) are one of the most important causes of sensorineural hearing loss, especially in the MT-RNR1 gene. In the present study we have performed mutational screening for m.1555A>G and a region of the MT-RNR1 gene in 303 unrelated patients (including family members of 25 probands) with nonsyndromic hearing loss and 200 controls.

High risk for essential hypertension in males conferred by g.15241A>G polymorphism in intron 3 of AGT gene.

A total of 180 hypertensive and 188 normotensive subjects were studied for demographic features and for variations in exon 4 including exon-intron boundary of AGT gene using single-strand conformation polymorphism analysis. Sequencing of the samples showing mobility shift revealed a single-nucleotide polymorphism variant g.15241A>G in intron 3 of the gene.

Migraine is associated with livedo reticularis: a prospective study.

Objective: To investigate the relationship of livedo reticularis, an ischemic dermatopathy, and migraine, an ischemic stroke risk factor.

Background: Livedo reticularis refers to the reddish-blue reticular mottling of the skin resulting from narrowing of small and medium arteries at the dermis-subcutis border. A subset of patients with livedo reticularis develop stroke in the absence of other vascular risk factors, which has been termed Sneddon syndrome.