Ellen Hertz1, Måns Thörnqvist2, Björn Holmberg3, Maciej Machaczka4,5, Ellen Sidransky6, Per Svenningsson1. 1. Section of Neurology, Department of Clinical Neuroscience Karolinska Institute Stockholm Sweden. 2. Section of Neurology Södra Älvsborg Hospital Borås Sweden. 3. Department of Clinical Neuroscience and Rehabilitation The Sahlgrenska Academy at University of Gothenburg Gothenburg Sweden. 4. Hematology Center Karolinska and Department of Medicine Huddinge Karolinska Institutet, Karolinska University Hospital Huddinge Stockholm Sweden. 5. Medical Faculty University of Rzeszow Rzeszow Poland. 6. Medical Genetics Branch National Human Genome Research Institute, National Institutes of Health Bethesda Maryland USA.
Abstract
BACKGROUND: Mutations in the glucocerebrosidase gene (GBA) are a common genetic risk factor for Parkinson's disease (PD). Mutations in the N-terminus part of GBA are less commonly found in association with PD than those in the C-terminus. Phenotypic characterization of GBA-related PD has been challenging, in part attributed to differential impact of distinct GBA mutations. AIM: To provide a phenotypic description of two patients with PD heterozygous for the GBA mutation S107L. The S107L mutation is located in the catalytic domain of glucocerebrosidase and has not previously been reported in patients with PD. METHODS: Motor and nonmotor symptoms (NMS) of PD were evaluated using established rating scales and questionnaires. The genotype was determined by Sanger sequencing. RESULTS: Two half-brothers, both heterozygous carriers of S107L, exhibited an early PD onset with several NMS. CONCLUSIONS: In these patients, heterozygosity for S107L was associated with an early onset of PD with NMS.
BACKGROUND: Mutations in the glucocerebrosidase gene (GBA) are a common genetic risk factor for Parkinson's disease (PD). Mutations in the N-terminus part of GBA are less commonly found in association with PD than those in the C-terminus. Phenotypic characterization of GBA-related PD has been challenging, in part attributed to differential impact of distinct GBA mutations. AIM: To provide a phenotypic description of two patients with PD heterozygous for the GBA mutation S107L. The S107L mutation is located in the catalytic domain of glucocerebrosidase and has not previously been reported in patients with PD. METHODS: Motor and nonmotor symptoms (NMS) of PD were evaluated using established rating scales and questionnaires. The genotype was determined by Sanger sequencing. RESULTS: Two half-brothers, both heterozygous carriers of S107L, exhibited an early PD onset with several NMS. CONCLUSIONS: In these patients, heterozygosity for S107L was associated with an early onset of PD with NMS.
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