Is the common
            <i>LRRK2</i>
            G2019S mutation related to dyskinesias in North African Parkinson disease?

Lesage, Suzanne; Belarbi, Soreya; Troiano, André R.; Condroyer, Christel; Hecham, Nassima; Pollak, Pierre; Lohman, Ebba; Benhassine, Traki; Ysmail-Dahlouk, Farida; Dürr, Alexandra; Tazir, Mériem; Brice, Alexis

doi:10.1212/01.wnl.0000338460.89796.06

Cited by 47 publications

(22 citation statements)

References 3 publications

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“…The p.Gly2019Ser mutation, although absent in more than 10,000 control individuals reported to date [Carmine Belin et al, 2006;Lesage et al, 2006;Ozelius et al, 2006;Papapetropoulos et al, 2006;Ross et al, 2006;Zabetian et al, 2006a], has also been identified in some asymptomatic individuals (16), of which one was 89 years old [Kay et al, 2005]. In addition, four clinically unaffected individuals of Algerian and Tunisian origin were found to be homozygous p.Gly2019Ser carriers (ages 41, 42, 45, and 70 years) [Ishihara et al, 2006;Lesage et al, 2008]. And although p.Arg1628Pro and p.Gly2385Arg variants are present in the control population with an overall frequency of 2.65% and 1.8%, respectively; they have been found to be significantly more prevalent in PD cases than in controls among individuals of Asian ancestries, suggesting that they act as risk factors for PD (Table 1).…”

Section: Mutations and Polymorphismsmentioning

confidence: 99%

LRRK2gene variation and its contribution to Parkinson disease

Paisán-Ruı́z

2009

Hum. Mutat.

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Mutation in the LRRK2 gene is a known genetic cause of Parkinson disease (PD). However, due to the high frequency in which the most frequent LRRK2 mutation is present and the large size of LRRK2 gene, a complete sequence-based screening of the entire coding region has only been performed by a few researchers. In addition, normal variability in the LRRK2 gene has only been fully assessed in the North American population. Although a complete examination of the entire gene is required to assess the exact contribution of LRRK2 to the etiology of PD, more than 50 variants have been reported to date within the LRRK2 locus. Gene multiplications or deletions have not been reported so far. Here, all LRRK2 variants reported are interpreted and their contribution to the disease is examined.

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Section: Mutations and Polymorphismsmentioning

confidence: 99%

LRRK2gene variation and its contribution to Parkinson disease

Paisán-Ruı́z

2009

Hum. Mutat.

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“…Frequencies ranged from the no cases to 35.7% in sporadic and 42% in familial North-African Arab patients (Brás et al 2005;Lesage et al 2005Lesage et al , 2006Lesage et al , 2008Clark et al 2006;Deng et al 2006;Gaig et al 2006;Goldwurm et al 2006;Infante et al 2006;Ozelius et al 2006;Marongiu et al 2006;Mata et al 2006Mata et al , 2009bCivitelli et al 2007;Cossu et al 2007;Ferreira et al 2007;González-Fernández et al 2007;Ishihara et al 2007;Orr-Urtreger et al 2007;Perez-Pastene et al 2007;Squillaro et al 2007;Hulihan et al 2008;Munhoz et al 2008;Pimentel et al 2008;Correia Guedes et al 2009;De Rosa et al 2009;Floris et al 2009;Gorostidi et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Analysis of Leucine-rich repeat kinase 2 (LRRK2) and Parkinson protein 2 (parkin, PARK2) genes mutations in Slovak Parkinson disease patients

Bognár¹,

Baldovič²,

Benetin³

et al. 2013

gpb

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Abstract. Parkinson disease (PD) is a chronic neurodegenerative movement disorder characterized by selective loss of nigrostriatal dopaminergic neurons and formation of Lewy bodies. Clinical manifestations include motor impairments involving tremor, bradykinesia, postural instability and rigidity.Using dHPLC method we screened exons 31, 35, 41, 48 of the Leucine-rich repeat kinase 2 (LRRK2) gene and exons 2, 6 and 7 of Parkinson protein 2 (parkin, PARK2) genes in a cohort of 216 consecutive, unrelated Slovak patients with familial or sporadic PD, including early and late onset. By this means we aimed to detect the most common pathogenic mutations within LRRK2 (Arg1441Cys, Arg1441Gly, Arg1628Pro, Tyr1699Cys, Gly2019Ser, Ile2020Thr, Gly2385Arg) and parkin genes responsible for late and early onset forms of disease, respectively. However, none of these mutations was identified in our cohort. Heterozygous point mutation p.Arg275Trp in exon 7 of parkin gene was identified in one patient with age at onset 61 years. Furthermore, we observed the presence of one exonic (LRRK2 ex 48: 7155A>G) and eight intronic polymorphisms (in LRRK2: IVS35+23T>A, IVS47-91insGCCAT, IVS47-91insGCAT, IVS47-41A>G, IVS47-9delT, IVS47-20C>T, IVS47-90A>G, in parkin: IVS2+25T>C), three of which were novel.

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“…Various studies have shown that the frequency of LRRK2 G2019S in North African populations is 30–42% in familial PD [3,4,5,6] and 30–34% in apparently sporadic PD [6,7]. Recently the international LRRK2 consortium reported a worldwide frequency of 1% of LRRK2 G2019S in ‘sporadic’ PD and 4% in familial PD, with the highest frequency of LRRK2 G2019S being observed in ‘North African Arabs’ (39% of sporadic and 36% of familial PD), consistent with the earlier observations [1].…”

Section: Lrrk2 G2019s In the North African Populationmentioning

confidence: 99%

“…Emerging data, however, seem to suggest that patients with the LRRK2 G2019S mutation from North Africa have a more severe motor phenotype, and especially more dyskinesias and drug-induced dyskinesias [6,9]. In the study by Lesage et al [6], levodopa-associated dyskinesias were more evident in G2019S carriers than in non-carriers, even after correction for (longer) treatment duration. These observations, if validated, may have diagnostic and therapeutic implications for clinical practice, as well as providing insights into the biological mechanisms underlying drug-induced motor complications.…”

Section: Lrrk2 G2019s In the North African Populationmentioning

confidence: 99%

<i>LRRK2</i> G2019S in the North African Population: A Review

Benamer

Silva

2010

Eur Neurol

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Parkinson’s disease (PD) is a common neurodegenerative disorder, for which environmental and/or genetic factors are postulated as possible causes. Over the past decade there has been a substantial increase in the knowledge of the genetics of PD. Mutations in Leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic causes of PD, and the common G2019S mutation has been identified in various ethnic groups with variable frequency. The aim of this article is to review the literature relating to LRRK2 G2019S in the North African population, which is composed of two main ethnic groups – the Berbers and the Arabs. The frequency of LRRK2 G2019S is 30–41% in familial PD and 30–39% in apparently sporadic PD in North Africa. Within healthy controls, Moroccan Berbers appear to have the highest carrier frequency at 3.3%. The majority of the available studies do not draw a clear distinction between the two ethnic groups, despite the distinct possibility that their ancestral origins are different. Further research looking at the respective prevalences of LRRK2 G2019S in Berbers and Arabs, and in different Arab populations, seems justified.

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Is the common LRRK2 G2019S mutation related to dyskinesias in North African Parkinson disease?

Cited by 47 publications

References 3 publications

LRRK2gene variation and its contribution to Parkinson disease

LRRK2gene variation and its contribution to Parkinson disease

Analysis of Leucine-rich repeat kinase 2 (LRRK2) and Parkinson protein 2 (parkin, PARK2) genes mutations in Slovak Parkinson disease patients

<i>LRRK2</i> G2019S in the North African Population: A Review

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