TY - JOUR
T1 - Parkinson's disease phenotype is influenced by the severity of the mutations in the GBA gene
AU - Thaler, Avner
AU - Bregman, Noa
AU - Gurevich, Tanya
AU - Shiner, Tamara
AU - Dror, Yonatan
AU - Zmira, Ofir
AU - Gan-Or, Ziv
AU - Bar-Shira, Anat
AU - Gana-Weisz, Mali
AU - Orr-Urtreger, Avi
AU - Giladi, Nir
AU - Mirelman, Anat
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Objective: Mutations in the glucocerebrosidase (GBA) gene are divided into mild and severe (mGBA, sGBA) based on their contribution to the phenotype of Gaucher disease (GD) among homozygotes. We conducted a longitudinal analysis of Parkinson's disease (PD) patients carrying mutations in the GBA gene to better characterize genotype-phenotype correlations. Methods: Patients underwent a comprehensive assessment of medical, neurological, cognitive and non-motor functions. Data from these patients was explored to evaluate differences in disease phenotype based on genotype. Results: A total of 355 PD patients participated in this study; 152 idiopathic PD patients, 139 mGBA, 48 sGBA and 16 GD-PD. Groups were similar in age, sex, years of education and age of onset. Both sGBA and GD-PD had higher Unified Parkinson Disease Rating Scale (UPDRS) scores (p = 0.041), higher frequencies of REM sleep behavior disorder (RBD) (p = 0.022) and hallucinations (p < 0.0001) compared to the other groups of patients. sGBA experienced more non-motor symptoms (p < 0.0001), depression (p < 0.001) and worse hyposmia (p = 0.010). Trail making test was significantly longer in GD-PD followed by sGBA, mGBA and iPD (p = 0.005). Discussion: Motor, cognitive, olfactory and psychiatric symptoms are more severe in sGBA and GD-PD compared to mGBA and iPD, reinforcing the notion that the severity of the PD phenotype is related to the severity of the mutation in the GBA gene.
AB - Objective: Mutations in the glucocerebrosidase (GBA) gene are divided into mild and severe (mGBA, sGBA) based on their contribution to the phenotype of Gaucher disease (GD) among homozygotes. We conducted a longitudinal analysis of Parkinson's disease (PD) patients carrying mutations in the GBA gene to better characterize genotype-phenotype correlations. Methods: Patients underwent a comprehensive assessment of medical, neurological, cognitive and non-motor functions. Data from these patients was explored to evaluate differences in disease phenotype based on genotype. Results: A total of 355 PD patients participated in this study; 152 idiopathic PD patients, 139 mGBA, 48 sGBA and 16 GD-PD. Groups were similar in age, sex, years of education and age of onset. Both sGBA and GD-PD had higher Unified Parkinson Disease Rating Scale (UPDRS) scores (p = 0.041), higher frequencies of REM sleep behavior disorder (RBD) (p = 0.022) and hallucinations (p < 0.0001) compared to the other groups of patients. sGBA experienced more non-motor symptoms (p < 0.0001), depression (p < 0.001) and worse hyposmia (p = 0.010). Trail making test was significantly longer in GD-PD followed by sGBA, mGBA and iPD (p = 0.005). Discussion: Motor, cognitive, olfactory and psychiatric symptoms are more severe in sGBA and GD-PD compared to mGBA and iPD, reinforcing the notion that the severity of the PD phenotype is related to the severity of the mutation in the GBA gene.
KW - GBA
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=85047185835&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2018.05.009
DO - 10.1016/j.parkreldis.2018.05.009
M3 - Article
C2 - 29784561
AN - SCOPUS:85047185835
SN - 1353-8020
VL - 55
SP - 45
EP - 49
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -