Neurology Department.
Geriatrics Department, Brugmann Hospital.
Alzheimer Dis Assoc Disord. 2024;38(4):328-331. doi: 10.1097/WAD.0000000000000643. Epub 2024 Aug 7.
Mutations in the LRRK2 gene are the most common genetic cause of Parkinson disease but are believed to play no significant role in Lewy body disease (LBD).
As the frequency of G2019S LRRK2 mutation is extremely high in North African patients with Parkinson disease, we postulate that the high prevalence of LBD in North Africa might be due to the same mutation because LBD and Parkinson disease share many clinical, pathological, and genetic features.
We screened patients with LBD or prodromal LBD for the G2019S mutation of LRRK2.
A total of 162 patients were tested for the mutation, which was present in 5 of the 47 patients with North African ancestors. This is a much higher prevalence (10.6%) than in healthy North African subjects (1.45%) but lower than in North African patients with Parkinson disease (36% to 39%). Carriers tended to develop more often orthostatic hypotension and swallowing problems.
Where previous studies in European and North American patients found no link between LRRK2 mutations and LBD, we found an LRRK2 mutation associated with Lewy body disease, namely the G2019S mutation that might be restricted to patients with North African ancestors. Our study illustrates the need to introduce ethnic diversity as stratifying factor in the analysis of genetic causes of neurodegenerative disorders. The current development of disease-modifying drugs modulating LRRK2 kinase activity could justify to screen North African patients with LBD for the G2019S LRRK2 mutation.
LRRK2 基因突变是帕金森病最常见的遗传原因，但据信其在路易体病（LBD）中不起重要作用。
由于北非帕金森病患者 G2019S LRRK2 突变的频率极高，我们推测北非 LBD 的高患病率可能是由于相同的突变引起的，因为 LBD 和帕金森病具有许多临床、病理和遗传特征。
我们筛选了 LBD 或前驱期 LBD 患者的 LRRK2 G2019S 突变。
共有 162 名患者接受了该突变的检测，在 47 名具有北非祖先的患者中有 5 名存在该突变。这一患病率（10.6%）明显高于健康北非人群（1.45%），但低于北非帕金森病患者（36%至 39%）。突变携带者更常出现直立性低血压和吞咽问题。
先前在欧洲和北美患者中的研究未发现 LRRK2 突变与 LBD 之间存在关联，而我们发现了一种与路易体病相关的 LRRK2 突变，即 G2019S 突变，该突变可能仅限于具有北非祖先的患者。我们的研究表明，需要将种族多样性作为分析神经退行性疾病遗传原因的分层因素引入。目前正在开发调节 LRRK2 激酶活性的疾病修饰药物，这可能证明对北非 LBD 患者进行 G2019S LRRK2 突变筛查是合理的。
