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.

LRRK2 mutations in Parkinson's disease : confirmation of a gender effect in the Italian population / R. Cilia, C. Siri, D. Rusconi, R. Allegra, A. Ghiglietti, G. Sacilotto, M. Zini, A.L. Zecchinelli, R. Asselta, S. Duga, A.M. Paganoni, G. Pezzoli, M. Seia, S. Goldwurm. - In: PARKINSONISM & RELATED DISORDERS. - ISSN 1353-8020. - 20:8(2014), pp. 911-914. [10.1016/j.parkreldis.2014.04.016]

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

A. Ghiglietti;
2014

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.
gender; genetics; LRRK2; Parkinson disease; aged; DNA mutational analysis; female; genetic predisposition to disease; heterozygote; humans; Italy; leucine-rich repeat serine-threonine protein kinase-2; male; middle aged; mutation; Parkinson disease; protein-serine-threonine kinases; sex characteristics; geriatrics and gerontology; neurology (clinical); neurology; medicine (all)
Settore BIO/11 - Biologia Molecolare
Settore SECS-S/01 - Statistica
Settore MED/01 - Statistica Medica
2014
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/464002
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