A Novel p.Glu298Lys Mutation in the ACMSD Gene in Sporadic Parkinson’s Disease

Abstract

Abstract.Background: Common genetic variability in the ACMSD gene has been associated with increased risk for Parkinson's disease (PD) but ACMSD mutations in clinical cases of PD have so far not been reported. Objective: To describe a case of sporadic PD carrying a novel ACMSD mutation. Methods: As part of a genetic study to identify potential pathogenic gene defects related to PD in the Mediterranean island Menorca, an initial group of 62 PD patients underwent mutational screening using a panel-based sequencing approach. Results: We report a 74-years-old man with sporadic PD who developed tremor in his right hand and slowness. On examination, moderate rigidity, asymmetric bradykinesia, and bilateral action tremor were present. He was started on levodopa with significant improvement. Two years later, he developed wearing off phenomena. The genetic study in the patient identified a novel ACMSD mutation resulting in p.Glu298Lys amino-acid change which was not present in neurologically normal population. Conclusions: Our data suggest that not only common genetic variability but also rare variants in ACMSD alone or in combination with other risk factors might increase the risk of PD.

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“…Several biological fluids are considered as the possible candidate for the detection of biomarkers that include blood, CSF and urine ( Table 2 ) [ 94 ]. Burgos et al [ 95 ] found that collection of CSF and serum, along with a complete evaluation of phenotypic conditions from PD patients, concluded that these biofluids reflected the exact cellular changes in diseased neuronal tissue.…”

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“…The missense mutation in the ACMSD gene predicted to disrupt enzyme function in typical PD individual, suggesting that this enzyme might influence PD pathogenesis ( 167 ). Vilas et al reported a novel ACMSD mutation resulting in the change of p.Glu298Lys amino-acid in a sporadic PD patient, which was not present in neurologically normal population, suggesting that not only common genetic variability but also rare variants in ACMSD alone might increase the risk of PD ( 182 ).…”

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“…Although ACMSD is normally expressed in the liver, kidney and brain, the disease primarily manifests as a neurological disorder in this family, suggesting an important role for ACMSD in the brain. Second , a novel p.Glu298Lys mutation in ACMSD was detected in a single individual with late onset (74 year-old) sporadic PD [ 22 ]. The individual was negative for other disease-causing mutations and had no first degree family history of PD.…”

“…Taken together, the two reports of mutations in the ACMSD gene that are associated with primary PD and PD-like symptoms suggest that reduced ACMSD function might confer PD risk. The fact that one disrupted allele of ACMSD might be sufficient to cause idiopathic PD in a patient is particularly strong evidence, implicating a role for this enzyme in PD pathogenesis [ 22 ]. However, there may be additional, unknown risk factors that might have contributed to PD pathology in this patient.…”