title: CAV3 gene sequence variations: National Genome Database and clinics.
abstract: BACKGROUND
  Caveolinopathies are a group of untreatable, degenerative muscle diseases associated with caveolin 3 (CAV3) gene mutations.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Latvian Biomedical Research and Study Center, Riga, Latvia.
authors: J
authors: http://orcid.org/0000-0002-0109-3312
authors: J
authors: Stavusis
authors: Latvian Biomedical Research and Study Center, Riga, Latvia.
authors: I
authors: I
authors: Inashkina
authors: Latvian Biomedical Research and Study Center, Riga, Latvia.
authors: E
authors: E
authors: Jankevics
authors: Latvian Biomedical Research and Study Center, Riga, Latvia.
authors: I
authors: I
authors: Radovica
authors: Latvian Biomedical Research and Study Center, Riga, Latvia.
authors: I
authors: I
authors: Micule
authors: Latvian Biomedical Research and Study Center, Riga, Latvia.
authors: J
authors: J
authors: Strautmanis
authors: Latvian Biomedical Research and Study Center, Riga, Latvia.
authors: M S
authors: MS
authors: Naudina
authors: Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.|Centre for Medical Genetics, Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania.
authors: A
authors: A
authors: Utkus
authors: Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.|Centre for Medical Genetics, Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania.
authors: B
authors: B
authors: Burnyte
authors: Latvian Biomedical Research and Study Center, Riga, Latvia.
authors: B
authors: B
authors: Lace
mesh_terms: D000328:Adult; D009202:Cardiomyopathies / Q000235:genetics; D051244:Caveolin 3 / Q000235:genetics*; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics; D009154:Mutation; D009468:Neuromuscular Diseases / Q000235:genetics*
chemical_list: C417736:CAV3 protein, human; D051244:Caveolin 3; D003402:Creatine Kinase
keywords: CAV3; LGMD1C; cardiomyopathy; caveolinopathy; hyperCKemia