RT Journal Article SR Electronic T1 Whole-exome sequencing associates novel CSMD1 gene mutations with familial Parkinson disease JF Neurology Genetics JO Neurol Genet FD Lippincott Williams & Wilkins SP e177 DO 10.1212/NXG.0000000000000177 VO 3 IS 5 A1 Javier Ruiz-Martínez A1 Luis J. Azcona A1 Alberto Bergareche A1 Jose F. Martí-Massó A1 Coro Paisán-Ruiz YR 2017 UL http://ng.neurology.org/content/3/5/e177.abstract AB Objective: Despite the enormous advancements made in deciphering the genetic architecture of Parkinson disease (PD), the majority of PD is idiopathic, with single gene mutations explaining only a small proportion of the cases.Methods: In this study, we clinically evaluated 2 unrelated Spanish families diagnosed with PD, in which known PD genes were previously excluded, and performed whole-exome sequencing analyses in affected individuals for disease gene identification.Results: Patients were diagnosed with typical PD without relevant distinctive symptoms. Two different novel mutations were identified in the CSMD1 gene. The CSMD1 gene, which encodes a complement control protein that is known to participate in the complement activation and inflammation in the developing CNS, was previously shown to be associated with the risk of PD in a genome-wide association study.Conclusions: We conclude that the CSMD1 mutations identified in this study might be responsible for the PD phenotype observed in our examined patients. This, along with previous reported studies, may suggest the complement pathway as an important therapeutic target for PD and other neurodegenerative diseases.AD=Alzheimer disease; CCP=complement control protein; fPD=familial Parkinson disease; H&Y=Hoehn and Yahr; INDEL=insertions/deletions; LOPD=late-onset PD; PD=Parkinson disease; RBD=REM sleep behavior disorder; RLS=restless legs syndrome; SNV=single nucleotide variant; WES=whole-exome sequencing