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 language | English |
|---|---|
| Pages (from-to) | 911-914 |
| Number of pages | 4 |
| Journal | Parkinsonism and Related Disorders |
| Volume | 20 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Gender
- Genetics
- LRRK2
- Parkinson disease
ASJC Scopus subject areas
- Geriatrics and Gerontology
- Clinical Neurology
- Neurology
Cite this
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 journal › Article
}
TY - JOUR
T1 - LRRK2 mutations in Parkinson's disease
T2 - Confirmation of a gender effect in the Italian population
AU - Cilia, Roberto
AU - Siri, Chiara
AU - Rusconi, Damiana
AU - Allegra, Roberta
AU - Ghiglietti, Andrea
AU - Sacilotto, Giorgio
AU - Zini, Michela
AU - Zecchinelli, Anna L.
AU - Asselta, Rosanna
AU - Duga, Stefano
AU - Paganoni, Anna M.
AU - Pezzoli, Gianni
AU - Seia, Manuela
AU - Goldwurm, Stefano
PY - 2014
Y1 - 2014
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.
KW - Gender
KW - Genetics
KW - LRRK2
KW - Parkinson disease
UR - http://www.scopus.com/inward/record.url?scp=84905273285&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905273285&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2014.04.016
DO - 10.1016/j.parkreldis.2014.04.016
M3 - Article
C2 - 24816003
AN - SCOPUS:84905273285
VL - 20
SP - 911
EP - 914
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
IS - 8
ER -