Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer.

Background: Next-Generation Sequencing (NGS)-based testing in cancer patients has led to increased detection of variants of uncertain significance (VUS). VUS are genetic variants whose impact on protein function is unknown. VUS pose a challenge to clinicians and patients due to uncertainty regarding their cancer predisposition risk.

Clinical Exome Gene Panel Analysis of a Cohort of Urothelial Bladder Cancer Patients from Sri Lanka.

Background: Bladder cancer has a high rate of recurrence and high mortality rates in those who progress to muscle invasive disease. Biomarkers and molecular sub classification of tumours beyond standard histopathology has been proposed to address therapeutic dilemmas. The Cancer Genome Atlas project and other studies have contributed to the enhanced knowledge base of the mutational landscape of urothelial bladder cancer.

Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes.

Background: Iron overload (IO) is a complication in transfusion dependent beta thalassaemia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka.

A novel variant in the COL6A1 gene causing Ullrich congenital muscular dystrophy in a consanguineous family: a case report.

Background: Collagen VI-related dystrophies are a subtype of congenital muscular dystrophy caused by pathogenic variants in COL6A1, COL6A2 or COL6A3 genes affecting skeletal muscles and connective tissue. The clinical phenotype ranges from the milder Bethlem myopathy to the severe Ullrich congenital muscular dystrophy (UCMD). Herein, we report the first consanguineous Sri Lankan family with two children affected with UCMD due to a novel variant in the COL6A1 gene.

Comparative Analysis of the Genetic Variants in Haematopoietic Stem/Progenitor and Mesenchymal Stem Cell Compartments in de novo Myelodysplastic Syndromes.

Myelodysplastic Syndromes (MDS) are hematological clonal disorders. Bone marrow (BM) mesenchymal stem cells (MSCs) interact with the haematopoietic stem and progenitor cells (HSPCs) to regulate haematopoiesis. We studied the genetic variation profiles of BM derived CD34 HSPCs and MSCs of same patient in a South Asian de novo MDS cohort with 20 patients.

Variant Profile of MECP2 Gene in Sri Lankan Patients with Rett Syndrome.

Rett syndrome (RTT) is a rare monogenic disorder affecting 1 in 10,000 live female births causing severe neurodegenerative symptoms. We analyzed the molecular genetic variants in the gene encoding the methyl-CpG binding protein 2 (MECP2) of 16 girls with RTT. Their mutation profile was as follows; Already described variants: p.

Genetic determinants of sporadic breast cancer in Sri Lankan women.

Background: While a range of common genetic variants have been identified to be associated with risk of sporadic breast cancer in several Western studies, little is known about their role in South Asian populations. Our objective was to examine the association between common genetic variants in breast cancer related genes and risk of breast cancer in a cohort of Sri Lankan women.

Methods: A case-control study of 350 postmenopausal women with breast cancer and 350 healthy postmenopausal women was conducted.

Implementation of genomic medicine in Sri Lanka: Initial experience and challenges.

The recent advances in next generation sequencing technologies have made it possible to implement genomic medicine in developing countries such as Sri Lanka where capacity for utilization is limited. This paper aims to describe our initial experience and challenges faced in integrating genomic medicine into routine clinical practice. Using the Illumina MiSeq Next generation sequencing (NGS) platform and an in-house developed bioinformatics pipeline/workflow, we successfully implemented clinical exome sequencing for rare disorders, complex disorders with unusual coexisting phenotypes, and multigene cancer panel testing for inherited cancer syndromes.

Association of HLA class I and II genes with cutaneous leishmaniasis: a case control study from Sri Lanka and a systematic review.

Background: The outcome of leishmaniasis is an interplay between Leishamania and the host. Identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. Leishmaniasis is caused exclusively by L.