title: Identification of novel variants in LRRK2 gene in patients with Parkinson's disease in Serbian population.
abstract: BACKGROUND
  Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common cause of autosomal dominant Parkinson's disease (PD). Large international studies have revealed that pathogenic mutations are clustered in several exons coding for functional domains of LRRK2 protein, but the mutation frequency differs among populations. Systematic study of LRRK2 mutation prevalence and phenotype in Serbian population has not been performed.
  
  
  METHODS
  Comprehensive mutation screening of selected exons of LRRK2 was performed in 486 Serbian PD patients.
  
  
  RESULTS
  Previously reported mutations I1371V and G2019S were identified in a single patient each, and c.4536+3A>G substitution in two patients. G2019S is the most common, pathogenic mutation, while pathogenic roles for recurrent variants I1371V and c.4536+3A>G are not confirmed yet. Two novel variants S1508G and I1991V were discovered in 2 unrelated patients. These variants are considered as disease causing according to several software predictions, but additional segregation and functional analyses are required.
  
  
  CONCLUSIONS
  Mutation frequency in our study (1.23%) was similar to other European populations, although the most common mutations were underestimated and novel variants were detected. In most cases, symptoms of LRRK2-PD are similar to sporadic PD, so estimation of frequency and penetrance of mutations in different populations is important for efficient genetic testing strategy and counseling.
authors.affiliation: Neurology Clinic, School of Medicine, University of Belgrade, Dr. Subotica 6, Belgrade, Serbia.
authors.forename: Milena Z
authors.initials: MZ
authors.lastname: Janković
authors.affiliation: Neurology Clinic, School of Medicine, University of Belgrade, Dr. Subotica 6, Belgrade, Serbia.
authors.forename: Nikola D
authors.initials: ND
authors.lastname: Kresojević
authors.affiliation: Neurology Clinic, School of Medicine, University of Belgrade, Dr. Subotica 6, Belgrade, Serbia.
authors.forename: Valerija S
authors.initials: VS
authors.lastname: Dobričić
authors.affiliation: Neurology Clinic, School of Medicine, University of Belgrade, Dr. Subotica 6, Belgrade, Serbia.
authors.forename: Vladana V
authors.initials: VV
authors.lastname: Marković
authors.affiliation: Neurology Clinic, School of Medicine, University of Belgrade, Dr. Subotica 6, Belgrade, Serbia.
authors.forename: Igor N
authors.initials: IN
authors.lastname: Petrović
authors.affiliation: Institute for Human Genetics, School of Medicine, University of Belgrade, Visegradska 26, Belgrade, Serbia.
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Novaković
authors.affiliation: Neurology Clinic, School of Medicine, University of Belgrade, Dr. Subotica 6, Belgrade, Serbia. Electronic address: vladimir.s.kostic@gmail.com.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostić
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D055771:Serbia / Q000453:epidemiology; D055815:Young Adult
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Genetics; LRRK2; Late onset; Mutation; PARK8; Parkinson's disease