Identification of Three Novel LRRK2 Mutations associated with Parkinson's Disease in a Calabrian Population

Article type: Research Article

Authors: Anfossi, Maria^{; 1} | Colao, Rosanna^{; 1} | Gallo, Maura^{; 1} | Bernardi, Livia | Conidi, M. Elena | Frangipane, Francesca | Vasso, Franca | Puccio, Gianfranco | Clodomiro, Alessandra | Mirabelli, Maria | Curcio, Sabrina A.M. | Torchia, Giusi | Smirne, Nicoletta | Di Lorenzo, Raffaele | Maletta, Raffaele | Bruni, Amalia C.^{; *}

Affiliations: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy

Correspondence: [*] Correspondence to: Dr. Amalia C. Bruni, Centro Regionale di Neurogenetica, Azienda Sanitaria Provinciale Catanzaro, Viale A. Perugini, 8046 Lamezia Terme (CZ), Italy. Tel.: +39 0968 208080; Fax: +39 0968 208032; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

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.

Keywords: Dementia, frequency mutations, genetics association, LRRK2, neurodegenerative disease, Parkinson's disease

DOI: 10.3233/JAD-130689

Journal: Journal of Alzheimer's Disease, vol. 38, no. 2, pp. 351-357, 2014