Friday 13 July 2018

Plain English - LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic

This research study compared patients with Parkinson's who carry the commonest gene mutation associated with the disease (called LRRK2), to patients with Parkinson's who do not carry this mutation. They found that on average patients with the mutation tended to have a milder form of Parkinson's (i.e. they had lower motor impairment scores and better scores on memory and other cognitive tests). 

Even though mutations in LRRK2 are the commonest genetic cause of Parkinson's, they are still pretty rare overall and affect about 1% of all patients with Parkinson's. This proportion is higher in North Africans (such as those in this study).

These findings in many ways match ones clinical impression as well. I would say on average patients with LRRK2 Parkinson's tend to have milder symptoms and a lower burden of non motor symptoms. These features may also be less prominent in the phase of the disease before diagnosis compared with Parkinson's that is not related to LRRK2. Of course, this is all 'on average'. On an individual basis it can be very tricky to choose between patients that do or don't have an underlying genetic cause, unless they are particular young when it starts or have a strong family history....

- Alastair Noyce

Acta Neurol Scand. 2018 Jul 10. doi: 10.1111/ane.12996. [Epub ahead of print]
Ben Romdhan S, Farhat N, Nasri A, Lesage S, Hdiji O, Ben Djebara M, Landoulsi Z, Stevanin G, Brice A, Damak M, Gouider R, Mhiri C.

https://onlinelibrary.wiley.com/doi/abs/10.1111/ane.12996

OBJECTIVES: The LRRK2-G2019S mutation is the most common cause of Parkinson's disease (PD) in North Africa. G2019S-PD has been described as similar to idiopathic with minor clinical differences. The aim of this study was to determine the G2019S-related phenotype and to investigate gender and gene dosage effects on clinical features of G2019S carriers.

PATIENTS AND METHODS: The G2019S mutation was screened in 250 Tunisian patients with PD. Twenty-four patients carrying mutations in other PD genes were excluded. Logistic regression models were used to compare clinical features between the studied groups.

RESULTS: G2019S carriers (107 cases) and non-carriers (119 cases) were similar in disease duration, levodopa doses, and gender and phenotype distributions. However, carriers had a younger age at examination, higher level of education, and were more likely to report family history of PD and to develop PD at earlier age (P = 0.017). Adjusted for age, sex, disease duration, levodopa-equivalent dose and educational level, MMSE scores remained significantly higher (adjust P = 0.019) and UPDRS-III scores were lower (adjust P = 0.012) in the G2019S carriers than non-carriers. Demographic characteristics of men and women with G2019S mutation were similar, but men had higher level of education, better cognition (adjust P-value for educational level = 0.042) and less tendency towards depression than females (adjust P = 0.046). Furthermore, PD phenotype did not differ between the homozygous and heterozygous G2019S carriers.

CONCLUSION: In this study, G2019S carriers had a more benign phenotype than non-carriers. Cognitive impairment and depression were less common in G2019S male carriers compared with females. In addition, we found that LRRK2 gene dosage does not influence the severity of PD.

1 comment:

  1. I just learned two months ago that I have the LRRK2 G2019s mutation. I have mixed ancestry with increased risk: North African, Berber, Ashkenazi Jewish. I have enrolled in the Parkinson's Progressive Marker Initiative among other clinical trials through the Michael J. Fox Foundation, with the goal of early (pre-clinical symptom) diagnosis. I am so happy/relieved to read the results of your study. I am eager to participate in any studies and education efforts that will promote and speed up early diagnosis, treatment and cure. Please let me know if I can be of any assistance in your efforts involving LRRK2 G2019s mutants and PD. I lost my sense of smell about 4.5 years ago and have other very subtle symptoms that are so subtle they are often easy to ignore. No diagnosis yet, frustrating to have to wait when I know something is going on and now that I know I have at least a 91% lifetime risk. Not to mention my father had PD. I am so glad to see the LRRK2 G2019s PD is usually more benign than its counterparts. Looking forward to posting a link to your blog on my new blog "Diary of a LRRK2 Mutant." Thank you for your research and your informative blog!!

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