Chang-He Shi1, Shu-Yu Zhang1, Zhi-Hua Yang1,2, Jing Yang1, Dan-Dan Shang3, Cheng-Yuan Mao1, Hao Liu4, Hai-Man Hou1, Meng-Meng Shi1, Jun Wu1, Yu-Ming Xu1. 1. Department of Neurology, The First affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China. 2. Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China. 3. Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China. 4. Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Abstract
OBJECTIVES: Mutations in RAB39B have been reported as a potential cause of X-linked Parkinson's disease (PD), a rare form of familial PD. We conducted a genetic analysis on RAB39B to evaluate whether RAB39B mutations are related to PD in the Chinese population. METHODS: In this study, 2 patients from an X-linked juvenile parkinsonism pedigree were clinically characterized and underwent whole-exome sequencing. A comprehensive screening for RAB39B mutations in 505 sporadic patients with PD and 510 healthy controls in a Chinese population was also performed. RESULTS: A novel mutation, c. 536dupA (p.E179fsX48), in RAB39B was identified in the juvenile parkinsonism pedigree. Brain MRI and CT scans in the 2 patients revealed calcification within the bilateral globus pallidus. No other potentially disease-causing RAB39B mutations were found in sporadic PD patients and controls. CONCLUSIONS: X-linked juvenile parkinsonism could be caused by a RAB39B mutation, and basal ganglia calcification may be a novel clinical feature of RAB39B-related parkinsonism.
OBJECTIVES: Mutations in RAB39B have been reported as a potential cause of X-linked Parkinson's disease (PD), a rare form of familial PD. We conducted a genetic analysis on RAB39B to evaluate whether RAB39B mutations are related to PD in the Chinese population. METHODS: In this study, 2 patients from an X-linked juvenile parkinsonism pedigree were clinically characterized and underwent whole-exome sequencing. A comprehensive screening for RAB39B mutations in 505 sporadic patients with PD and 510 healthy controls in a Chinese population was also performed. RESULTS: A novel mutation, c. 536dupA (p.E179fsX48), in RAB39B was identified in the juvenile parkinsonism pedigree. Brain MRI and CT scans in the 2 patients revealed calcification within the bilateral globus pallidus. No other potentially disease-causing RAB39B mutations were found in sporadic PDpatients and controls. CONCLUSIONS:X-linked juvenile parkinsonism could be caused by a RAB39B mutation, and basal ganglia calcification may be a novel clinical feature of RAB39B-related parkinsonism.
Authors: Shekeeb S Mohammad; Rajeshwar Reddy Angiti; Andrew Biggin; Hugo Morales-Briceño; Robert Goetti; Belen Perez-Dueñas; Allison Gregory; Penelope Hogarth; Joanne Ng; Apostolos Papandreou; Kaustuv Bhattacharya; Shamima Rahman; Kristina Prelog; Richard I Webster; Evangeline Wassmer; Susan Hayflick; John Livingston; Manju Kurian; W Kling Chong; Russell C Dale Journal: Brain Commun Date: 2020-10-26