Familial parkinson disease A comparative study between LRRK2 and PINK 1 mutations - MDS Ab

Objective: Describe the clinical phenotypes of monogenic forms of PD linked to LRRK2 and PINK1 mutations with a view to a comparative study between the two phenotypes.describe the clinical phenotypes of monogenic forms of PD linked to LRRK2 and PINK1 mutations with a view to a comparative study between the two phenotypes.

Background: The G2019S mutation in the LRRK2 gene was the most common, with a particularly high prevalence among Berber Arabs (40% in Tunisia). On the other hand, PINK1gene mutations are significant contributors to early-onset PD in north Africa.

Method: This retrospective study included 158 patients from the department of neurology of the National Institute of Neurology Mongi Ben Hmida in Tunis, Tunisia, diagnosed with familial PD (FPD) between 1980 and 2023 and having benefited from a genetic study. Among them, we selected those with the LRRK2 mutation and PINK1 mutation. All patients have completed the Case Report Form (CRF), providing information on demographic data, interrogation and evaluation scales of motor and non-motor signs of the PD.

Results: We included 66 patients with an LRRK2 mutation and 18 with a PINK1 mutation. In both groups, patients were predominantly males (M/F=0.94 vs 0.38; p=0.18). in the PINK1 group, patients were younger (64.95±12.49 vs 55.83±9.19; p=0.005) and had an earlier onset (54.39±11.50 vs 36.06±6.73; p=0.0001). Regarding motor symptoms, no significant difference was found between both groups (On state: 36.00±19.11vs 29.00±12.44; p=0.252/ Off state: 52.47±24.37 vs 40.67±19.79; p=0.266). Nevertheless, the PINK1 group had a less severe score on facial expression (p=0.050), while intention tremor was less severe in the LRRK2 group (p=0.020). Comparing non-motor signs, constipation, gastrointestinal disorders and cognitive disorders were significantly more severe in the LRRK2 group (p=0.009, p=0.010 and p=0.030 respectively) and male sexual disorders were significantly more common in the PINK1 group (p=0.043). According to the Schwab and England scale, the PINK 1 group had a significantly less severe form than the LRKK2 group (p=0.012) and the time to progression of PD was significantly longer in the PINK 1 (19.78±9.31) compared with LRRK2 (10.56±7.42) (p=0.0001).

Conclusion: Ten to 30% of PD patients have a familial monogenic form. A comparative study of the monogenic forms will help to standardise and guide genetic research, especially in developing countries.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/familial-parkinson-disease-a-comparative-study-between-lrrk2-and-pink-1-mutations/