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LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic.
Acta Neurol Scand 2018; 138(5):425-431AN

Abstract

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.

Authors+Show Affiliations

Laboratory of Neurogenetics, Parkinson's Disease and Cerebrovascular Disease, University Hospital Habib Bourguiba, Sfax, Tunisia. Institut du Cerveau et de la Moelle épinière, INSERM U1127, Sorbonne Université, UPMC Paris VI Univ. UMR_S1127, CNRS UMR 7225, Paris, France. École Pratique des Hautes Études EPHE, PSL Research University, Paris, France.Laboratory of Neurogenetics, Parkinson's Disease and Cerebrovascular Disease, University Hospital Habib Bourguiba, Sfax, Tunisia.Department of Neurology, University Hospital Razi, Tunis, Mannouba, Tunisia.Institut du Cerveau et de la Moelle épinière, INSERM U1127, Sorbonne Université, UPMC Paris VI Univ. UMR_S1127, CNRS UMR 7225, Paris, France.Laboratory of Neurogenetics, Parkinson's Disease and Cerebrovascular Disease, University Hospital Habib Bourguiba, Sfax, Tunisia.Department of Neurology, University Hospital Razi, Tunis, Mannouba, Tunisia.Department of Neurology, University Hospital Razi, Tunis, Mannouba, Tunisia.Institut du Cerveau et de la Moelle épinière, INSERM U1127, Sorbonne Université, UPMC Paris VI Univ. UMR_S1127, CNRS UMR 7225, Paris, France. École Pratique des Hautes Études EPHE, PSL Research University, Paris, France.Institut du Cerveau et de la Moelle épinière, INSERM U1127, Sorbonne Université, UPMC Paris VI Univ. UMR_S1127, CNRS UMR 7225, Paris, France.Laboratory of Neurogenetics, Parkinson's Disease and Cerebrovascular Disease, University Hospital Habib Bourguiba, Sfax, Tunisia.Department of Neurology, University Hospital Razi, Tunis, Mannouba, Tunisia.Laboratory of Neurogenetics, Parkinson's Disease and Cerebrovascular Disease, University Hospital Habib Bourguiba, Sfax, Tunisia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29989150

Citation

Ben Romdhan, Sawssan, et al. "LRRK2 G2019S Parkinson's Disease With More Benign Phenotype Than Idiopathic." Acta Neurologica Scandinavica, vol. 138, no. 5, 2018, pp. 425-431.
Ben Romdhan S, Farhat N, Nasri A, et al. LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic. Acta Neurol Scand. 2018;138(5):425-431.
Ben Romdhan, S., Farhat, N., Nasri, A., Lesage, S., Hdiji, O., Ben Djebara, M., ... Mhiri, C. (2018). LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic. Acta Neurologica Scandinavica, 138(5), pp. 425-431. doi:10.1111/ane.12996.
Ben Romdhan S, et al. LRRK2 G2019S Parkinson's Disease With More Benign Phenotype Than Idiopathic. Acta Neurol Scand. 2018;138(5):425-431. PubMed PMID: 29989150.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic. AU - Ben Romdhan,Sawssan, AU - Farhat,Nouha, AU - Nasri,Amina, AU - Lesage,Suzanne, AU - Hdiji,Olfa, AU - Ben Djebara,Mouna, AU - Landoulsi,Zied, AU - Stevanin,Giovanni, AU - Brice,Alexis, AU - Damak,Mariem, AU - Gouider,Riadh, AU - Mhiri,Chokri, Y1 - 2018/07/10/ PY - 2018/01/07/received PY - 2018/06/21/accepted PY - 2018/7/11/pubmed PY - 2018/12/12/medline PY - 2018/7/11/entrez KW - G2019S mutation KW - Parkinson's disease KW - phenotype SP - 425 EP - 431 JF - Acta neurologica Scandinavica JO - Acta Neurol. Scand. VL - 138 IS - 5 N2 - 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. SN - 1600-0404 UR - https://www.unboundmedicine.com/medline/citation/29989150/LRRK2_G2019S_Parkinson's_disease_with_more_benign_phenotype_than_idiopathic_ L2 - https://doi.org/10.1111/ane.12996 DB - PRIME DP - Unbound Medicine ER -