ABSTRACT
INTRODUCTION: Caveolinopathies are a group of untreatable, degenerative muscle diseases associated with caveolin 3 (CAV3) gene mutations. OBJECTIVES: The goal of this study was to characterize the role of the CAV3 gene in patients with limb-girdle muscular dystrophy, hyperCKemia, cardiomyopathies, as well as utilization of the National Genome Database in clinical applications. MATERIALS AND METHODS: We sequenced the coding region and exon/intron boundaries of CAV3 gene in 81 neuromuscular disorder patients, a sample group from the National Genome Database, consisting of 97 individuals with cardiomyopathies, and also random selection of 100 persons. Immunohistochemical staining of muscle biopsy was performed to verify findings in one case, as the setup for the project was to use less invasive molecular biology methods. RESULTS: We identified three novel sequence variations (c.183C>G, p.S61R; c.220C>A, p.R74S; c.220C>T, p.R74C) and found evidence that one was associated with hypercreatine kinase-emia. Two previously reported mutations in families with limb-girdle muscular dystrophy were found. No mutations were identified in the cohort of patients with cardiomyopathies. DISCUSSION: CAV3 gene encodes muscle-specific protein with dominant negative type of missense mutations in it causing various phenotypes. Our study confirmed CAV3 gene involvement in neuromuscular disorders, but found no evidence in the group of patients with cardiomyopathies. Persons included in the National Genome Database could be screened for late onset Mendelian diseases.
Subject(s)
Caveolin 3/genetics , Neuromuscular Diseases/genetics , Adult , Cardiomyopathies/genetics , Creatine Kinase/blood , Female , Humans , Male , Middle Aged , Muscular Dystrophies, Limb-Girdle/genetics , MutationABSTRACT
BACKGROUND: Abnormal lipid levels are considered one of the most significant risk factors for atherosclerosis and coronary artery disease, two of the main causes of death worldwide. Apart from monogenic cases of hypercholesterolemia, most of the common dyslipidemias are caused by a number of low-impact polymorphisms. It has recently been reported that frequent polymorphisms at a large number of loci are significantly associated with one or more blood lipid parameters in many populations. Identifying these associations in different populations and estimating the possible interactions between genetic models are necessary to explain the underlying genetic architecture of the associated loci and their ultimate impact on lipid-associated traits. METHODS: We estimated the association between 144 common single-nucleotide polymorphisms (SNPs) from published genome-wide association studies and the levels of total cholesterol, low- and high-density lipoprotein-cholesterol, and triglycerides in 1273 individuals from the Genome Database of the Latvian Population. We analyzed a panel of 144 common SNPs with Illumina GoldenGate Genotyping Assays on the Illumina BeadXpress System. RESULTS: Ten SNPs at the CETP locus and two at the MLXIPL locus were associated with reduced high-density lipoprotein-cholesterol levels; one SNP at the TOMM40 locus was associated with increased low-density lipoprotein-cholesterol; and four SNPs at the MLXIPL locus were associated with increased log triglyceride levels. There was also a significant correlation between the number of risk alleles and all the lipid parameters, suggesting that the coexistence of many low-impact SNPs has a greater effect on the dyslipidemia phenotype than the individual effects of found SNPs. CONCLUSION: We conclude that the CETP, MLXIPL, and TOMM40 loci are the strongest genetic factors underlying the variability in lipid traits in our population.
ABSTRACT
BACKGROUND: Essential tremor (ET) is the most prevalent inherited movement disorder. ET has been mapped on chromosomes 2 and 3, but causative genes are not known. METHODS: We genotyped 16 microsatellite markers in a case-control cohort consisting of 104 patients and 116 controls. RESULTS: No significant difference between allele frequencies was found. The highest difference of frequencies was found in allele 171 of the marker D2S220 (OR 0.13, 95% CI 0.02-1.03, P = 0.05). In addition, we investigated the distribution of suspected disease gene DRD3 Ser9Gly polymorphism in the same patients and controls. CONCLUSION: There was not a significant difference in genotypic distribution between disease group and control subjects (chi2 =2.8, P = 0.25).
