LRRK2 mutations in Parkinson's disease: Confirmation of a gender effect in the Italian population

Roberto Cilia, Chiara Siri, Damiana Rusconi, Roberta Allegra, Andrea Ghiglietti, Giorgio Sacilotto, Michela Zini, Anna L. Zecchinelli, Rosanna Asselta, Stefano Duga, Anna M. Paganoni, Gianni Pezzoli, Manuela Seia, Stefano Goldwurm

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Abstract

The relative risk of developing idiopathic PD is 1.5 times greater in men than in women, but an increased female prevalence in LRRK2-carriers has been described in the Ashkenazi Jewish population. We report an update about the frequency of major LRRK2 mutations in a large series of consecutive patients with Parkinson's disease (PD), including extensive characterization of clinical features. In particular, we investigated gender-related differences in motor and non-motor symptoms in the LRRK2 population. Methods: 2976 unrelated consecutive Italian patients with degenerative Parkinsonism were screened for mutations on exon 41 (G2019S, I2020T) and a subgroup of 1190 patients for mutations on exon 31 (R1441C/G/H). Demographic and clinical features were compared between LRRK2-carriers and non-carriers, and between male and female LRRK2 mutation carriers. Results: LRRK2 mutations were identified in 40 of 2523 PD patients (1.6%) and not in other primary parkinsonian syndromes. No major clinical differences were found between LRRK2-carriers and non-carriers. We found a novel I2020L missense variant, predicted to be pathogenic. Female gender was more common amongst carriers than non-carriers (57% vs. 40%; p=0.01), without any gender-related difference in clinical features. Family history of PD was more common in women in the whole PD group, regardless of their LRRK2 status. Conclusions: PD patients with LRRK2 mutations are more likely to be women, suggesting a stronger genetic load compared to idiopathic PD. Further studies are needed to elucidate whether there is a different effect of gender on the balance between genetic and environmental factors in the pathogenesis of PD.

Original languageEnglish
Pages (from-to)911-914
Number of pages4
JournalParkinsonism and Related Disorders
Volume20
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Parkinson Disease
Mutation
Population
Parkinsonian Disorders
Exons
Genetic Load
Demography

Keywords

  • Gender
  • Genetics
  • LRRK2
  • Parkinson disease

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

Cite this

Cilia, R., Siri, C., Rusconi, D., Allegra, R., Ghiglietti, A., Sacilotto, G., ... Goldwurm, S. (2014). LRRK2 mutations in Parkinson's disease: Confirmation of a gender effect in the Italian population. Parkinsonism and Related Disorders, 20(8), 911-914. https://doi.org/10.1016/j.parkreldis.2014.04.016

LRRK2 mutations in Parkinson's disease : Confirmation of a gender effect in the Italian population. / Cilia, Roberto; Siri, Chiara; Rusconi, Damiana; Allegra, Roberta; Ghiglietti, Andrea; Sacilotto, Giorgio; Zini, Michela; Zecchinelli, Anna L.; Asselta, Rosanna; Duga, Stefano; Paganoni, Anna M.; Pezzoli, Gianni; Seia, Manuela; Goldwurm, Stefano.

In: Parkinsonism and Related Disorders, Vol. 20, No. 8, 2014, p. 911-914.

Research output: Contribution to journalArticle

Cilia, R, Siri, C, Rusconi, D, Allegra, R, Ghiglietti, A, Sacilotto, G, Zini, M, Zecchinelli, AL, Asselta, R, Duga, S, Paganoni, AM, Pezzoli, G, Seia, M & Goldwurm, S 2014, 'LRRK2 mutations in Parkinson's disease: Confirmation of a gender effect in the Italian population', Parkinsonism and Related Disorders, vol. 20, no. 8, pp. 911-914. https://doi.org/10.1016/j.parkreldis.2014.04.016
Cilia, Roberto ; Siri, Chiara ; Rusconi, Damiana ; Allegra, Roberta ; Ghiglietti, Andrea ; Sacilotto, Giorgio ; Zini, Michela ; Zecchinelli, Anna L. ; Asselta, Rosanna ; Duga, Stefano ; Paganoni, Anna M. ; Pezzoli, Gianni ; Seia, Manuela ; Goldwurm, Stefano. / LRRK2 mutations in Parkinson's disease : Confirmation of a gender effect in the Italian population. In: Parkinsonism and Related Disorders. 2014 ; Vol. 20, No. 8. pp. 911-914.
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abstract = "The relative risk of developing idiopathic PD is 1.5 times greater in men than in women, but an increased female prevalence in LRRK2-carriers has been described in the Ashkenazi Jewish population. We report an update about the frequency of major LRRK2 mutations in a large series of consecutive patients with Parkinson's disease (PD), including extensive characterization of clinical features. In particular, we investigated gender-related differences in motor and non-motor symptoms in the LRRK2 population. Methods: 2976 unrelated consecutive Italian patients with degenerative Parkinsonism were screened for mutations on exon 41 (G2019S, I2020T) and a subgroup of 1190 patients for mutations on exon 31 (R1441C/G/H). Demographic and clinical features were compared between LRRK2-carriers and non-carriers, and between male and female LRRK2 mutation carriers. Results: LRRK2 mutations were identified in 40 of 2523 PD patients (1.6{\%}) and not in other primary parkinsonian syndromes. No major clinical differences were found between LRRK2-carriers and non-carriers. We found a novel I2020L missense variant, predicted to be pathogenic. Female gender was more common amongst carriers than non-carriers (57{\%} vs. 40{\%}; p=0.01), without any gender-related difference in clinical features. Family history of PD was more common in women in the whole PD group, regardless of their LRRK2 status. Conclusions: PD patients with LRRK2 mutations are more likely to be women, suggesting a stronger genetic load compared to idiopathic PD. Further studies are needed to elucidate whether there is a different effect of gender on the balance between genetic and environmental factors in the pathogenesis of PD.",
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AU - Ghiglietti, Andrea

AU - Sacilotto, Giorgio

AU - Zini, Michela

AU - Zecchinelli, Anna L.

AU - Asselta, Rosanna

AU - Duga, Stefano

AU - Paganoni, Anna M.

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N2 - The relative risk of developing idiopathic PD is 1.5 times greater in men than in women, but an increased female prevalence in LRRK2-carriers has been described in the Ashkenazi Jewish population. We report an update about the frequency of major LRRK2 mutations in a large series of consecutive patients with Parkinson's disease (PD), including extensive characterization of clinical features. In particular, we investigated gender-related differences in motor and non-motor symptoms in the LRRK2 population. Methods: 2976 unrelated consecutive Italian patients with degenerative Parkinsonism were screened for mutations on exon 41 (G2019S, I2020T) and a subgroup of 1190 patients for mutations on exon 31 (R1441C/G/H). Demographic and clinical features were compared between LRRK2-carriers and non-carriers, and between male and female LRRK2 mutation carriers. Results: LRRK2 mutations were identified in 40 of 2523 PD patients (1.6%) and not in other primary parkinsonian syndromes. No major clinical differences were found between LRRK2-carriers and non-carriers. We found a novel I2020L missense variant, predicted to be pathogenic. Female gender was more common amongst carriers than non-carriers (57% vs. 40%; p=0.01), without any gender-related difference in clinical features. Family history of PD was more common in women in the whole PD group, regardless of their LRRK2 status. Conclusions: PD patients with LRRK2 mutations are more likely to be women, suggesting a stronger genetic load compared to idiopathic PD. Further studies are needed to elucidate whether there is a different effect of gender on the balance between genetic and environmental factors in the pathogenesis of PD.

AB - The relative risk of developing idiopathic PD is 1.5 times greater in men than in women, but an increased female prevalence in LRRK2-carriers has been described in the Ashkenazi Jewish population. We report an update about the frequency of major LRRK2 mutations in a large series of consecutive patients with Parkinson's disease (PD), including extensive characterization of clinical features. In particular, we investigated gender-related differences in motor and non-motor symptoms in the LRRK2 population. Methods: 2976 unrelated consecutive Italian patients with degenerative Parkinsonism were screened for mutations on exon 41 (G2019S, I2020T) and a subgroup of 1190 patients for mutations on exon 31 (R1441C/G/H). Demographic and clinical features were compared between LRRK2-carriers and non-carriers, and between male and female LRRK2 mutation carriers. Results: LRRK2 mutations were identified in 40 of 2523 PD patients (1.6%) and not in other primary parkinsonian syndromes. No major clinical differences were found between LRRK2-carriers and non-carriers. We found a novel I2020L missense variant, predicted to be pathogenic. Female gender was more common amongst carriers than non-carriers (57% vs. 40%; p=0.01), without any gender-related difference in clinical features. Family history of PD was more common in women in the whole PD group, regardless of their LRRK2 status. Conclusions: PD patients with LRRK2 mutations are more likely to be women, suggesting a stronger genetic load compared to idiopathic PD. Further studies are needed to elucidate whether there is a different effect of gender on the balance between genetic and environmental factors in the pathogenesis of PD.

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