Advocating Targeted Sequential Screening over Whole Exome Sequencing in 21-Hydroxylase Deficiency.

Objectives: Whole exome sequencing (WES) has emerged as the preferred method for diagnosing a range of Mendelian disorders. Nonetheless, the applicability of WES in genetic diagnosis of 21-hydroxylase deficiency (21-OHD) remains uncertain due to the intricacies involved in molecular analysis of the CYP21A2 gene.

Methods: In this case series, authors report the outcomes of couples or families who underwent WES followed by focused sequential strategy (FSS) targeting CYP21A2 gene hotspot mutations and targeted sequencing of genes associated with Congenital Adrenal Hyperplasia (CAH).

Congenital Adrenal Hyperplasia - A Comprehensive Review of Genetic Studies on 21-Hydroxylase Deficiency from India.

Congenital adrenal hyperplasia (CAH) comprises a heterogeneous group of autosomal recessive disorders impairing adrenal steroidogenesis. Most cases are caused by mutations in the gene resulting in 21-hydroxylase (21-OH) deficiency (21-OHD). The genetics of 21-OH CAH is complexed by a highly homologous pseudogene imposing several limitations in the molecular analysis.

Clinical, Hormonal, and Genetic Spectrum of 46 XY Disorders of Sexual Development (DSD) Patients.

Objectives: To evaluate the clinical, hormonal and genetic characteristics of 46XY disorders of sexual development (DSD) patients from South India.

Methods: 46XY DSD patients with a provisional diagnosis of 17β-hydroxysteroid dehydrogenase 3 (17BHSD3) deficiency, 5 alpha-reductase type 2 deficiency (5ARD2) or partial androgen insensitivity syndrome (PAIS) based on clinical and hormonal analysis were included in this study. All the patients underwent detailed clinical and hormonal evaluations.

The BRCA mutation spectrum among breast and ovarian cancers in India: highlighting the need to screen BRCA1 185delAG among South Indians.

Mutations in BRCA1 and BRCA2 significantly elevate the risk of developing breast and ovarian cancer. Limited data exists regarding the prevalence of BRCA mutations, and optimal, cost-effective testing strategies in developing countries like India. This study aimed to evaluate the utility of a Next Generation Sequencing (NGS) panel for BRCA1/2 mutation testing among women diagnosed with, or at risk of developing hereditary breast and ovarian cancers.

High carrier frequency of CYP21A2 gene mutations in Southern India - underscoring the need for genetic testing in Congenital Adrenal Hyperplasia.

Purpose: Congenital Adrenal Hyperplasia (CAH) is one of the highly prevalent autosomal recessive endocrine disorders. The majority of CAH cases result from mutations in the CYP21A2 gene, leading to 21-hydroxylase deficiency. However, with the pseudogene-associated challenges in CYP21A2 gene analysis, routine genetic diagnostics and carrier screening in CAH are not a part of the first-tier investigations in a clinical setting.

Clinical Features of Unrecognized Congenital Adrenal Hyperplasia Due to 17α-hydroxylase Deficiency Since Adolescence: A Case Report.

The majority of patients with congenital adrenal hyperplasia (CAH) present with a deficiency of 21-hydroxylase or 11-beta-hydroxylase, which account for 90% and 7% of cases, respectively. However, CAH due to 17α-hydroxylase deficiency (17OHD) is an extremely rare form of CAH (<1% of all CAH cases) that leads to a deficiency of cortisol and sex steroids, along with features of aldosterone excess. This is a case of a 51-year-old single female who was referred to us for the evaluation of new-onset hypertension and hypokalaemia of one-year duration.

WFS1 Gene-associated Diabetes Phenotypes and Identification of a Founder Mutation in Southern India.

Context: Wolfram syndrome (WFS) is a rare autosomal recessive disorder characterized by juvenile-onset diabetes, diabetes insipidus, optic atrophy, deafness, and progressive neurodegeneration. However, due to the progressive nature of the disease and a lack of complete clinical manifestations, a confirmed diagnosis of WFS at the time of onset of diabetes is a challenge.

Objective: With WFS1 rare heterozygous variants reported in diabetes, there is a need for comprehensive genetic screening strategies for the early diagnosis of WFS and delineating the phenotypic spectrum associated with the WFS1 gene variants in young-onset diabetes.

Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India.

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India.

Incidence, Intrapartum Risk Factors, and Prognosis of Neonatal Hypoxic-Ischemic Encephalopathy Among Infants Born at 35 Weeks Gestation or More.

Introduction: Neonatal hypoxic-ischemic encephalopathy (HIE) is associated with neonatal mortality, acute neurological injury, and long-term neurodevelopmental disabilities; however, the association between intrapartum factors and HIE remains unclear.

Methods: This population-based cohort study used linked obstetrical and newborn data derived from the Nova Scotia Atlee Perinatal Database (NSAPD, 1988-2015) and the AC Allen Perinatal Follow-Up Program Database (2006-2015) for all pregnancies with live, non-anomalous newborns ≥35 weeks gestation, not delivered by pre-labour cesarean section. Temporal trends in HIE incidence were described, and logistic regression estimated odds ratios (OR) with 95% confidence intervals (CI) for the association of intrapartum factors with HIE.

Epitope-based immunoinformatics approach on RNA-dependent RNA polymerase (RdRp) protein complex of Nipah virus (NiV).

Persistent outbreaks of Nipah virus (NiV) with severe case fatality throw a major challenge on researchers to develop a drug or vaccine to combat the disease. With little knowledge of its molecular mechanisms, we utilized the proteome data of NiV to evaluate the potency of three major proteins (phosphoprotein, polymerase, and nucleocapsid protein) in the RNA-dependent RNA polymerase complex to count as a possible candidate for epitope-based vaccine design. Profound computational analysis was used on the above proteins individually to explore the T-cell immune properties like antigenicity, immunogenicity, binding to major histocompatibility complex class I and class II alleles, conservancy, toxicity, and population coverage.

Non-alcoholic fatty liver disease and outcomes in persons with acute coronary syndromes: insights from the GRACE-ALT analysis.

Objective: Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of cardiovascular disease, but no data exist about the relation between NAFLD and adverse outcomes in persons with acute coronary syndromes (ACS). We evaluated elevated serum alanine aminotransferase (ALT) as a marker of NAFLD, in association adverse outcomes following ACS.

Methods: We conducted a retrospective cohort study of participants enrolled in the Global Registry of Acute Coronary Events (GRACE) admitted for ACS to St Michael's Hospital, Toronto, between 1999 and 2007.