Haplotype analysis detects MLH1 founder variant in Indian Lynch syndrome patient cohort.

Lynch syndrome (LS) is an autosomal dominant hereditary cancer predisposition syndrome whereby the lifetime risk of developing gastrointestinal and genitourinary cancers rises by to over 50%. It is caused by heterozygous variants in the DNA mismatch repair genes- MLH1, MSH2, MSH6 and PMS2, with the majority detected in MLH1 and MSH2. Recurrently observed LS-associated variants in apparently unrelated individuals have either arisen de novo in different families due to mutation hotspots or are inherited from a common ancestor (founder) that lived several generations back.

Does Prior Nasal Airway Surgery Impact Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea?

Objective: Nasal surgery can improve patient-reported obstructive sleep apnea (OSA) outcomes as well as adherence with medical device treatments. The aim of this study was to examine whether previous nasal surgery was associated with hypoglossal nerve stimulation (HNS) therapy outcomes.

Study Design: Retrospective observational cohort study was performed utilizing the multicenter international HNS registry (ADHERE).

Progressive Supranuclear Palsy in India: Past, Present, and Future.

Progressive supranuclear palsy (PSP) has emerged as a key area of interest among researchers worldwide, including those in India, who have actively studied the disorder over the past several decades. This review meticulously explores the extensive range of Indian research on PSP up to the present and offers insights into both current initiatives and potential future directions for managing PSP within the region. Historical research contributions have spanned 80 publications from 1974 to 2023, encompassing diverse themes from clinical phenotyping and historical analysis to isolated investigative studies and therapeutic trials.

Comprehensive germline profiling of patients with breast cancer: initial experience from a Familial Cancer Clinic.

Introduction: Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India.

Objective: The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC).

Identification of a shared, common haplotype segregating with an SGCB c.544 T > G mutation in Indian patients affected with sarcoglycanopathy.

Sarcoglycanopathy is the most frequent form of autosomal recessive limb-girdle muscular dystrophies caused by mutations in SGCB gene encoding beta-sarcoglycan proteins. In this study, we describe a shared, common haplotype co-segregating in 14 sarcoglycanopathy cases from 13 unrelated families from south Indian region with the likely pathogenic homozygous mutation c.544 T > G (p.

South Asian medical cohorts reveal strong founder effects and high rates of homozygosity.

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes.

Comprehensive laboratory diagnosis of Fanconi anaemia: comparison of cellular and molecular analysis.

Background: Fanconi anaemia (FA) is a rare inherited bone marrow failure disease caused by germline pathogenic variants in any of the 22 genes involved in the FA-DNA interstrand crosslink (ICL) repair pathway. Accurate laboratory investigations are required for FA diagnosis for the clinical management of the patients. We performed chromosome breakage analysis (CBA), FANCD2 ubiquitination (FANCD2-Ub) analysis and exome sequencing of 142 Indian patients with FA and evaluated the efficiencies of these methods in FA diagnosis.

Genotype-phenotype correlation and natural history study of dysferlinopathy: a single-centre experience from India.

Dysferlinopathies are a group of limb-girdle muscular dystrophies causing significant disability in the young population. There is a need for studies on large cohorts to describe the clinical, genotypic and natural history in our subcontinent. To describe and correlate the clinical, genetic profile and natural history of genetically confirmed dysferlinopathies.

Molecular epidemiology of SARS-CoV-2 in healthcare workers and identification of viral genomic correlates of transmissibility and vaccine break through infection: A retrospective observational study from a cancer hospital in eastern India.

Purpose: Despite COVID vaccination with ChAdOx1 ncov-19 (COVISHIELD®) (ChAdOx1 ncov-19) a large number of healthcare workers (HCWs) were getting infected in wave-2 of the pandemic in a cancer hospital of India. It was important therefore to determine the genotypes responsible for vaccine breakthrough infections.

Methods & Objectives: Retrospective observational study of HCWs.

Spectrum and management of breast cancer patients with variant of uncertain significance mutations at a tertiary care centre in North India.

Background: The spectrum and significance of Variants of Uncertain Significance (VUS) mutations in breast cancer predisposition genes is poorly defined in the Indian population.

Methods: All new female breast cancer patients from 1 March 2019 to 28 February 2020 were screened. Those providing informed consent and without previous genetic testing were recruited.

Genome-Wide Polygenic Score Predicts Large Number of High Risk Individuals in Monogenic Undiagnosed Young Onset Parkinson's Disease Patients from India.

Parkinson's disease (PD) is a genetically heterogeneous neurodegenerative disease with poorly defined environmental influences. Genomic studies of PD patients have identified disease-relevant monogenic genes, rare variants of significance, and polygenic risk-associated variants. In this study, whole genome sequencing data from 90 young onset Parkinson's disease (YOPD) individuals are analyzed for both monogenic and polygenic risk.

Factors affecting obstructive sleep apnea patients' use of upper airway stimulation treatment.

Study Objectives: Upper airway stimulation (UAS) is an alternative treatment for obstructive sleep apnea that must be activated nightly. Although the implanted device offsets the mask- or pressure-related side effects often associated with continuous positive airway pressure therapy, some UAS recipients do not use the therapy consistently. This study qualitatively explored factors associated with UAS usage in obstructive sleep apnea patients.

Clinical, genetic profile and disease progression of sarcoglycanopathies in a large cohort from India: high prevalence of SGCB c.544A > C.

The clinico-genetic architecture of sarcoglycanopathies in Indian patients is reported only as short series. In the present study, we aimed to investigate the clinical picture, genetic basis, and disease progression of patients genetically confirmed to have sarcoglycanopathy. Next-generation sequencing was performed in 68 probands with suspected sarcoglycanopathy.

Quality of Life in Patients With Recurrent and Second Primary Head and Neck Cancer.

Objective: In the setting of similar outcomes, quality of life (QOL) measures can be utilized to compare treatment modalities in head and neck squamous cell carcinoma (HNSCC). We evaluate QOL and symptoms in patients treated for primary, second primary, and recurrent HNSCC.

Study Design: Retrospective cohort study.

Operative Surveillance of Airway Hemangiomas in PHACE Syndrome.

Objective: PHACE is a rare syndrome that can present with airway hemangiomas. Management for these patients is variable and the utilization of operative endoscopic airway evaluation has not been described. The objectives of this study were to identify the incidence of airway symptoms in patients being evaluated for PHACE syndrome and determine the utility of operative endoscopy.

Cost analysis of sialendoscopy for the treatment of salivary gland disorders in children.

Introduction: Recent advances in Otolaryngology have changed the diagnosis and therapy for salivary gland disorders. Sialendoscopy-assisted surgery is a minimally invasive, conservative procedure for functional preservation of the affected gland. The goals of this study are to assess the indications, use, and outcomes of pediatric sialendoscopy at a tertiary pediatric institution as well as to analyze the direct cost related to the diagnosis and treatment of patients with sialolithiasis and Juvenile Recurrent Parotitis managed with sialendoscopy.

Growth and neurodevelopmental disorder with arthrogryposis, microcephaly and structural brain anomalies caused by Bi-allelic partial deletion of SMPD4 gene.

Neutral sphingomyelinases have an important role in generation of ceramide and phosphorylcholine from sphingomyelins which then act as secondary messengers in various signaling pathways of the cellular machinery. They function ubiquitously with a predominant role in the central nervous system. Neutral sphingomyelinase type 3, encoded by SMPD4 gene has recently been reported to cause a severe autosomal recessive neurodevelopmental disorder with congenital arthrogryposis and microcephaly.

Profile of Pathogenic Mutations and Evaluation of Germline Genetic Testing Criteria in Consecutive Breast Cancer Patients Treated at a North Indian Tertiary Care Center.

Background: The burden of hereditary breast cancer in India is not well defined. Moreover, genetic testing criteria (National Comprehensive Cancer Network [NCCN] and Mainstreaming Cancer Genetics [MCG] Plus) have never been validated in the Indian population.

Methods: All new female breast cancer patients from 1st March 2019 to 28th February 2020 were screened.