A considerable proportion of Lynch syndrome families present with mismatch repair (MMR) gene sequence variants of uncertain clinical significance, which constitute a challenge in both the research and clinical settings. Such unclassified variants (UVs) include rare nucleotide changes predicted to cause missense substitutions, small in-frame deletions, or possible alterations in splicing. We are...

mutations in the human hepatitis b virus (hbv) genome contribute to its escape from host immune surveillance and result in persistent infections. the aim of this study was to characterize the molecular variations of the surface gene and protein in chronically-infected patients from the southern part of iran. the  surface  genes  from  12  hbv  chronic  carriers  were  amplified, sequenced  and ...

Mutations in the ATP13A2 gene (PARK9) cause autosomal recessive, juvenile-onset Kufor-Rakeb syndrome (KRS), a neurodegenerative disease characterized by parkinsonism. KRS mutations produce truncated forms of ATP13A2 with impaired protein stability resulting in a loss-of-function. Recently, homozygous and heterozygous missense mutations in ATP13A2 have been identified in subjects with early-onse...

The Long QT syndrome (LQTS) is a disorder characterized by a prolongation of the QT interval and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death. Our objective was to (1) determine the incidence of variants with unknown significance (VUS) in a cohort of consecutive LQTS patients and (2) to determine the percentage of those with novel miss...

The assessment of the influence of many rare BRCA2 missense mutations on cancer risk has proved difficult. A multifactorial likelihood model that predicts the odds of cancer causality for missense variants is effective, but is limited by the availability of family data. As an alternative, we developed functional assays that measure the influence of missense mutations on the ability of BRCA2 to ...

Cholesterol is essential for development, growth, and maintenance of organisms. Mutations in cholesterol biosynthetic genes are embryonic lethal and few polymorphisms have been so far associated with pathologies in humans. Previous analyses show that lanosterol 14α-demethylase (CYP51A1) from the late part of cholesterol biosynthesis has only a few missense mutations with low minor allele freque...

introduction: autosomal dominant polycystic kidney disease (adpkd) is one of the most common genetic kidney disorders with the incidence of 1 in 1,000 births. adpkd is genetically heterogeneous with two genes identified: pkd1 (16p13.3, 46 exons) and pkd2 (4q21, 15 exons). eighty five percent of the patients with adpkd have at least one mutation in the pkd1 gene. genetic studies have demonstrate...

Classification of rare missense substitutions observed during genetic testing for patient management is a considerable problem in clinical genetics. The Bayesian integrated evaluation of unclassified variants is a solution originally developed for BRCA1/2. Here, we take a step toward an analogous system for the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) that confer colon cancer su...

The susceptibility gene for ataxia telangiectasia, ATM, is also an intermediate-risk breast-cancer-susceptibility gene. However, the spectrum and frequency distribution of ATM mutations that confer increased risk of breast cancer have been controversial. To assess the contribution of rare variants in this gene to risk of breast cancer, we pooled data from seven published ATM case-control mutati...

Sickle cell disease is an autosomal recessive hematological disorder resulting from a missense point mutation in the beta chain of haemoglobin molecule. This article reports case homozygous sickle adult patient with long-standing history non-healing ulcer