title: Identification of three novel LRRK2 mutations associated with Parkinson's disease in a Calabrian population.
abstract: BACKGROUND
  LRRK2 mutations are common in familial and sporadic Parkinson's disease (PD) cases.
  
  
  OBJECTIVE
  We present a screening of the most frequently mutated exons of LRRK2 in Calabrian population.
  
  
  METHODS
  Eighty-eight PD patients diagnosed according to standard criteria, underwent screening for LRRK2 mutations in exons 19, 21, 24, 25, 27, 29, 31, 32, 33, 35, 38, 40, 41, and 48.
  
  
  RESULTS
  Eight LRRK2 variations were identified in nine patients affected by PD, including three novel missense variations (p.Phe1227Leu, p.Gly1520Ala, p.Ile2020Ser) and five previously identified mutations (p.Ala1151Thr, IVS31+3A>G, p.Arg1514Gln, p.Gly2019Ser, p.Thr2356Ile). LRRK2 frequency mutations were approximately 10.2% in all PD patients, 12% in familial, 8% in sporadic cases. The p.Gly2019Ser mutation was found in 2.3% of the total cohort and in 3.2% of sporadic cases. The clinical features of LRRK2-associated with PD in our patients were similar to those of idiopathic PD although most LRRK2 mutated patients presented with bradykinesia instead of tremor; 33.3% developed dementia.
  
  
  CONCLUSIONS
  We identified three novel LRRK2 mutations and reported a higher frequency in Calabria compared to previously reported data possibly due to the relative genetic isolation of the Calabrian population. These findings contribute to the understanding of the role of LRKK2 variations in PD and provide additional genetic insight into this disease.
authors: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors: Maria
authors: M
authors: Anfossi
authors: Rosanna
authors: R
authors: Colao
authors: Maura
authors: M
authors: Gallo
authors: Livia
authors: L
authors: Bernardi
authors: M Elena
authors: ME
authors: Conidi
authors: Francesca
authors: F
authors: Frangipane
authors: Franca
authors: F
authors: Vasso
authors: Gianfranco
authors: G
authors: Puccio
authors: Alessandra
authors: A
authors: Clodomiro
authors: Maria
authors: M
authors: Mirabelli
authors: Sabrina A M
authors: SA
authors: Curcio
authors: Giusi
authors: G
authors: Torchia
authors: Nicoletta
authors: N
authors: Smirne
authors: Raffaele
authors: R
authors: Di Lorenzo
authors: Raffaele
authors: R
authors: Maletta
authors: Amalia C
authors: AC
authors: Bruni
mesh_terms: D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007558:Italy; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000208:ethnology* / Q000235:genetics*; D044382:Population Groups / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Dementia; LRRK2; Parkinson's disease; frequency mutations; genetics association; neurodegenerative disease